Hemin inhibits NO production by IL-1beta-stimulated human astrocytes through induction of heme oxygenase-1 and reduction of p38 MAPK activation

Seems to me that the findings from this author are pretty important....:)

"up-regulation of HO-1 in astrocytes is associated with down-regulation of iNOS expression and thereby NO production, an effect that involves the p38 MAPK signaling pathway, which suggests that this glial cell response could play an important protective role against oxidative stress in the brain."

"Sheng, W., Hu, S., Nettles, A., Lokensgard, J., Vercellotti, G., and Rock, R. (2010). Hemin inhibits no production by il-1beta-stimulated human astrocytes through induction of heme oxygenase-1 and reduction of p38 mapk activation. Journal of Neuroinflammation, 7(1):51+."

Read more: CiteULike: Hemin inhibits NO production by IL-1beta-stimulated human astrocytes through induction of heme oxygenase-1 and reduction of p38 MAPK activation:

Gulf War Syndrome, Chemical Sensitivity and Why Benefits of CPAP!

It has only been in the not-to-distant past that officials and medical experts have come out and admitted that Gulf War Syndrome is an actual disease and while many that have tried to find the cause the "true cause" is not yet known. In previous blogs, I have discussed how Gulf War Syndrome shares many of the same symptoms as other environmental conditions and are often co-morbid and include chronic fatigue syndrome, fibromyalgia and multiple chemical sensitivity and other environmental factors may contribute to fascilitate the condition that is commonly regarded as Gulf War Syndrome. One well-respected research blogger, Dr. Art Ayers, explains that CFS, MCS and fibromyalgia "can be induced by organophosphate pesticide exposure. In GWS, two insults seem to be needed: acetylcholine signal disruption and inflammation. He says that in the effected individuals the acetylcholine mimetics (pesticides, pyridostigmine) disrupted the nervous system and numerous immunological, infectious, chemical and emotional stresses generated a high level of chronic inflammation. The vaccine against anthrax and exposure to burning oil wells may have contributed to inflammation." Without a clear understanding of what causes GWS, physicians and health experts are mostly at a loss on how to treat it and clearly, most of the research is now focused on providing effective therapies until a cure is found for it.

In recent weeks, two interesting studies have been released that show CPAP (continuous positive airway pressure) may be beneficial in treating symptoms of Gulf War Syndrome with sleep disordered breathing. In the pilot study, findings demonstrated improvements in many symptoms including pain, fatigue, cognitive function, sleep quality, physical and mental health. The researchers' concluded from this experiment that CPAP can greatly improve overall health in GW patients with sleep disordered breathing which may be a distinguishing factor in veterans with GWI compared to veterans without Gulf War Illness. (Amin)  While this research is preliminary it provides interesting insight into GWS. Admittedly, there are reported side-effects associated with CPAP use and the pros and cons of it should be addressed fully with a qualified physician even if CPAP is taken out of the research lab and used as therapy for GWS.

To date, even with these published findings, the reader is left with the question why CPAP may be effective for treating some symptoms of GWS. The author only makes the comment that GWS experience a "frequency of arousals related to apneas, hypopneas, and mild inspiratory airflow limitation."  Taking a more holistic systematic approach to understanding the nature of GWS ; one can draw some conclusions that provide at least a reasonable explanation of what may be occurring in GW patients with sleep apneas and why CPAP may provide at least "some" relief. CPAP has been used for quite some time to  treat sleep apneas and more recently has been used for a variety of other medical respiratory conditions. Budhiraja explains that sleep disordered breathing is often associated with hypertension and that "sleep apnea, hypocapneas and hypoxemia contribute to alterations in sympathetic activity, changes in the renin-angiotensin pathway, impede xanthine oxireductase production, cause endothelial dysfunction and lower levels of eNOS."  If you are a consistent reader of my feeds, chronic low-level inflammation contributes to endothelial dysfunction and higher risk for cardiovascular disease in many environmentally-induced health conditions.

Recently, it has been suggested that sickness syndrome contributes to symptoms in GWS and may explain  fatigue, pain and other behavioral changes as well. Sickness syndrome is in associated with elevated levels of cytokines including Il-1b and Il-6 and these inflammatory cytokines may also be associated with PTSD and CFS and are activated during the general response to stress which can lead to changes in genetic expression. Two researchers, Burioka and Steiropoulis found significant changes in Il-6 and Tnf-a, uric acid and immune complexes after CPAP. These findings suggest intermittent hypoxia contibutes significantly to inflammation and noted positive changes in patients that use regularly CPAP .  We have suggested that insulin resistance may be a critical factor in environmental illness and obesity and dietary influences may influence the severity of many environmental diseases including sickness syndrome, PTSD, MCS, CFS and fibromyalgia. To some extent, this can be explained by the fact that inflammatory cytokines and adipokines such as leptin and adiponectin can produce systemic changes. Patients with OSA have a higher prevalence of insulin resistance both in the obese and non-obese. (Lam)

In severa studies, agents such as pesticides, particulates and compounds emitted from fires and other environmental conditions that GW veterans may have been exposed too, exert an inhibitory and/or negative influence on cell function. (Gulati) For example, the metabolites of many toxic chemicals consistent with these types of exposures bio-accumulate in adipose tissue and contribute to inflammation and insulin resistance. (Nov) More specifically, it is proposed immune-mediate macrophages in adipose tissue contribute to insulin resistance and Tregs dampen this response and their reduction may contribute to insulin resistance. (Winer) Also, smaller particulates that bind to metals and hydrocarbons and contain endotoxin may infiltrate deeply into body tissues and through a complex process, end up in vessels and contribute to inflammation that leads to vascular disease.  (Li) An August 2010 study of Gulf War patients demonstrate high prevalence of problems with hypercoagulation which are also common in sleep apnea patients and can potentially be reversed by use of CPAP in some individuals. (Guardiola, Nichols)

Sleep apnea often accompanies obesity and for years, it has been assumed that inflammation is an important consequence of obesity. However, many experts now believe endothelial inflammation probably precedes obesity. Whatever the case may be, CPAP has demonstrated therapeutic effects on inflammation in obesity and this inflammatory process is similar in other environmentally-induced diseases. This leads one to assume its benefits may be achieved in the same way for GWS patients. Budhiraja and others have shown,  "CPAP therapy improves endothelial function, decreases the abnormally increased levels of circulating apoptotic endothelial cells, attenuates free radical production from neutrophils and monocytes, reduces the levels of C-reactive protein (CRP), a marker of vascular inflammation, increases vasodilator levels and mediates a decline in vasoconstrictor levels  in patients with sleep apnea altering blood flow. In the future, more studies may demonstrate CPAP may be of benefit for other "somatic" environmental illnesses as well.  (Gold, El Soth) In CPAP studies in obese patients, CPAP therapy has shown to reduce oxidative stress as well as, raise levels of SOD and alter nitrate and nitrite levels. Other changes that are reflected during CPAP adjustments also may have positive influences on physiology in a so-far unknown way. (Calero)

I have agreed with a few health experts and proposed due to my own experiences with several environmental diseases, severe reactions of MCS may be caused by the "lack of tolerance" to environmental conditions. Reactions develops to conditions that were considered normal and therefore, is more like an autoimmune disease and inflammatory cytokines and epigenetic changes in gene expression are contributory to this disruption. This "loss of tolerance" could explain why MCS patients develop extreme sensitivity to very low levels of pollutants such as those found in perfumes and detergents. Chemical sensitivity is also common in Gulf War veterans but the research disagrees with the Treg theory at least in part. Interestingly, a recent study demonstrated that post-natal exposure to flame retardents in animals leads to inhibitory functions on the AhR and a reduction of Tregs (Wahl)  and supports that the AhR modulates Treg production (Mezrich) and they may  be a factor at least in some types of reactions to certain toxins.  It would be interesting to examine different Treg ratios and to compare them with patients with MCS that are not GW patients and also compare this to other factors. Specifically, one example would be extenuating circumstances that dramatically effect stress response regulation. From my own experience, I would suggest actual stress and anxiety levels may alter certain markers because my own reactions are significantly different in different environments.

As far as chemical sensitivity, the idea of "loss of tolerance" is relatively new and may involve a better understanding of a "bridge" that links the immune system and metabolic homeostasis.  Because glucose and metabolic dysregulation seems to be concurrent with many environmental illnesses, one must consider metabolic syndrome as a risk factor for any environmental illness and there is little doubt some may contribute to GWS.  Hersoug hypothesizes that diseases like atopy, asthma and autoimmune diseases which are more common with obesity are the result of changes in adipokines including leptin, adiponectin, Il-6 and tumor necrosis factor (Tnf-a) secreted by white adipose tissue.  He adds that body weight contributes to an increase of these inflammatory mediators which in turn down-regulate regulatory T cells which in turn results in a reduction of the anti-inflammatory Il-10. He proposes that this process forms the basis of the idea of "loss of tolerance" and this author believes the loss of "Tregs" contributes significantly to chemical and environmental pollutant sensitivity. Other factors such as endotoxin and loss by genetics or environmental depression of Nrf2 and aberrant AhR signalling may augment the inflammation and allergic and non-allergic reactions and responses and may explain some of the sensitivity to "oil fires".  This may partially be explained by the fact that crude oil and coal dust contain significant amounts of polyaromatic hydrocarbons (PAH) and are ligands for the AhR. (Neff)  They are present in high amounts in diesel exhaust and disruption of the Nrf2 raises allergic airway inflammatory reactions to oxidative stress at much lower levels of diesel exhaust exposure. This may be true and does not dismis some reactions may be a consequence of diesel hydrocarbon content. (Li) Quinatana concludes the AhR, depending on the ligand, is able to modulate both Tregs and Il-17 which is often upregulated in inflammatory autoimmune diseases. It is easy to gather from all of this, that there is probably no simple answer to resolution of environmental disease except to prevent and limit exposures to the "activating" agents.

Of course, one needs to consider the initial "trigger" and the resulting inflammatory immune response may be different through time and be altered through interaction with other other chronic environmental and behavioral factors such as exercise, diet and other noxious "agents" of exposure in one's environment.  The AhR may provide a clue or two because of its role in activation from dioxins and its aberrant signals could be enough to initiate inflammatory responses that may be important in GWS and chemical sensitivity. I have proposed that some of this is due to the communication channel between the Nrf2 and the AhR. Jensen explains that exposure to PAH AhR ligands suppress B cell production and suppress Il-6 and makes an important comment that any alteration in Il-6 can lead to assorted pathologies including autoimmune disease, vitiligo, lupus and multple sclerosis.  Under normal conditions, elevations in Il-6 increase significantly through time in response to endotoxin but when cells are exposed to dioxin or another AhR ligand, cells presented with much lower levels of Il-6. Jensen concludes, "Any environmental chemical capable of compromising this response has the potential to disrupt the regulation of many important stromal cell functions, including generation of inflammatory responses in general and the elaboration of several cytokines, including IL-6, to regulate blood cell development in particular."  In addition, Jensen's research shows that exposures of different AhR ligands including PAH which are prevalent both in indoor and outdoor environments may be different depending on the tissue and may lead to elevations in other inflammatory cytokines such as Tnf-a. Considering that these influences are common in the environment, they can serve to augment responses in GWS or any environmental disease for that matter. (Jensen) One potential consideration is that if alterations in cytokines contribute to blood abnormalities that contribute to hypoxic conditions,
improvements observed with CPAP may reflect improvements in blood parameters of one sort or another. (Incidentally, after my last chemical injury obvious symptoms could have been explained by blood abnormalities like these. Unfortunately, they were not diagnosed because of improper medical care by a licensed practitioner and brings up concerns about access to properly trained practioners for environmental disease which I have discussed at length in other blogs.)

Foster shows that impaired regulation to hypoxic condition in sleep apnea patients and CPAP increases blood flow to normal levels. Another study demonstrates "hypoxia and dioxin response pathways can compete for limiting cellular factor(s) and cross-talk that occur between the hypoxia and dioxin signal transduction pathways and identify Epo as an AHR-regulated gene." (Chan)  This suggests signal dysfunction may influence a battery of physiological and toxicological responses. Most recently in fish, there is evidence that hypoxia reduces the response of the AhR. (Matson) This brings to light two important concerns in light of the discussion here. One is that there is direct interaction between the AhR and the Nrf2 antioxidant system and two, the AhR is an activator of Tregs regulation. In this context, dysfunction could certainly lead to apneas and chronic inflammation. It also may lead to other impairments in the antioxidant system and possibly to chemical sensitivities with a lower Treg production and a "loss of tolerance". It is also worth pondering the extent of effects of blood cell production in relation to circadian rhythm and influence on the positive effects of CPAP (Burioka).

An alternative example of aberrant levels of Il-6 demonstrates the complexity of environmental disease in relation to inflammatory mediators. Curiously, a recent report shows how different factors may be instrumental and  suggest that stress and the effect of pyridostigmine bromide (PB) may be a plausible cause of GWS. Mauck says that his research shows that while stress normally upregulates muscarinic receptor density, the application of  pyridostigmine bromide or physostigmine reduces them. One of the muscarinic targets is the Nrf2 and may suggest a reduction in these receptors may also reduce or prevent the activation of Nrf2. In addition, GSK-3b inhibition also augments muscarinic signals and Treg expression. Thus, conditions where GSK-3b is upregulated may have a negative influence on both chemical sensitivity in GWS and also other types of chemical sensitivity.  The other part of the puzzle in these conditions may be explained and supported by evidence that shows pesticides may contribute to insulin resistance and diabetes and may negatively influence how the body reacts to infection. This could alter inflammatory mediator production and in turn, contribute to the neuroinflammatory process as shown through reductions of Il-6 by GSk-3b inhibition.(Beurel) Dioxins on the other hand, seem to contribute to insulin resistance independant of the AhR. (Hsu)

I have often said in other blogs that environmental illnesses seem more like a failure to adapt and the concept of down-regulation of Tregs provides a viable mechanism for "maladaptation" at least in multiple chemical sensitivity. It may end up that taking genetic expression and immune regulators into account could be what differentiates the forms of chemical sensitivity in autism and MCS from GWS. If Amin is correct and the presence of apneas can be a predictor of  GW syndrome, then one can presume dysregulation of glucose metabolism similar to that that would occur with obesity and the development of chronic inflammation even though GW patients may not be overweight may contribute to GWS. Obesity is a problem in all age groups and classes and is associated with Western diets and GSK-3b may also play its part. It is worth considering that Gulf War veterans that are overweight and eat a typical Western diet will be more at risk for more severe GWI symptoms and those with conditions that depress Nrf2 (which are often diet, exposure and epigenetic influences related) will be even more so!  One may suggest that a lifestyle that promotes healthy eating and low-inflammatory menu like a Mediterranean diet may provide some healthy benefits.





Amin, M. M., Belisova, Z., Hossain, S., Gold, M. S., Broderick, J. E., and Gold, A. R. (2010). Inspiratory airflow dynamics during sleep in veterans with gulf war illness: a controlled study. Sleep & breathing = Schlaf & Atmung. http://www.citeulike.org/user/HEIRS/article/7756111
Gold, A. R., Dipalo, F., Gold, M. S., and Broderick, J. (2004). Inspiratory airflow dynamics during sleep in women with fibromyalgia. Sleep, 27(3):459-466. http://www.citeulike.org/user/HEIRS/article/7756324
Omurtag, G. Z., Tozan, A., Sehirli, A. O. O., and Sener, G. (2008). Melatonin protects against endosulfan-induced oxidative tissue damage in rats. Journal of pineal research, 44(4):432-438.  http://www.citeulike.org/user/HEIRS/article/2674835
Gulati, K., Banerjee, B., Lall, S. B., and Ray, A. (2010). Effects of diesel exhaust, heavy metals , and pesticides on various organ systems: Possible mechanisms and strategies for prevention and treatment. Indian Journal of Experimental Biology, 48:710-721. http://www.citeulike.org/user/HEIRS/article/7753532
Calero, G., Farre, R., Ballester, E., Hernandez, L., Daniel, N., and Montserrat Canal, J. M. (2006). Physiological consequences of prolonged periods of flow limitation in patients with sleep apnea hypopnea syndrome. Respiratory medicine, 100(5):813-817. http://www.citeulike.org/user/HEIRS/article/7756347
Singh, A. K. and Jiang, Y. Lipopolysaccharide (lps) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate. Toxicology and Industrial Health, 19(2-6):93-108. http://www.citeulike.org/user/HEIRS/article/7796
Li, R., Ning, Z., Cui, J., Yu, F., Sioutas, C., and Hsiai, T. (2010). Diesel exhaust particles modulate vascular endothelial cell permeability: implication of zo-1 expression. Toxicology letters, 197(3):163-168.  http://www.citeulike.org/user/HEIRS/article/7284279
Nov, O., Kohl, A., Lewis, E. C., Bashan, N., Dvir, I., Ben-Shlomo, S., Fishman, S., Wueest, S., Konrad, D., and Rudich, A. (2010). Interleukin-1beta may mediate insulin resistance in liver-derived cells in response to adipocyte inflammation. Endocrinology, 151(9):4247-4256. http://www.citeulike.org/user/HEIRS/article/7752881
Budhiraja, R. and Quan, S. F. (2009). When is cpap an antihypertensive in sleep apnea patients? Journal of clinical sleep medicine : JCSM, 5(2):108-109. http://www.citeulike.org/user/HEIRS/article/7752952
Amin, M. M., Gold, M. S., Broderick, J. E., and Gold, A. R. (2010). The effect of nasal continuous positive airway pressure on the symptoms of gulf war illness. Sleep & breathing = Schlaf & Atmung. http://www.citeulike.org/user/HEIRS/article/7756404
Hersoug, L.-G. G., Husemoen, L. L., Sigsgaard, T., Madsen, F., and Linneberg, A. (2010). Indoor exposure to environmental cigarette smoke, but not other inhaled particulates associates with respiratory symptoms and diminished lung function in adults. Respirology (Carlton, Vic.), 15(6):993-1000.  http://www.citeulike.org/user/HEIRS/article/7582695
Hersoug, L.-G. G. and Linneberg, A. (2007). The link between the epidemics of obesity and allergic diseases: does obesity induce decreased immune tolerance? Allergy, 62(10):1205-1213. http://www.citeulike.org/user/HEIRS/article/1640991
Winer, S., Chan, Y., Paltser, G., Truong, D., Tsui, H., Bahrami, J., Dorfman, R., Wang, Y., Zielenski, J., Mastronardi, F., Maezawa, Y., Drucker, D. J., Engleman, E., Winer, D., and Dosch, H.-M. M. (2009). Normalization of obesity-associated insulin resistance through immunotherapy. Nature medicine, 15(8):921-929. http://www.citeulike.org/user/HEIRS/article/5398151
El Solh, A. A., Akinnusi, M. E., Baddoura, F. H., and Mankowski, C. R. (2007). Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction. American journal of respiratory and critical care medicine, 175(11):1186-1191.  http://www.citeulike.org/user/HEIRS/article/7756664
Burioka, N., Miyata, M., Fukuoka, Y., Endo, M., and Shimizu, E. (2008). Day-night variations of serum interleukin-6 in patients with severe obstructive sleep apnea syndrome before and after continuous positive airway pressure (cpap). Chronobiology international, 25(5):827-834. http://www.citeulike.org/user/HEIRS/article/7748469
Steiropoulos, P., Kotsianidis, I., Nena, E., Tsara, V., Gounari, E., Hatzizisi, O., Kyriazis, G., Christaki, P., Froudarakis, M., and Bouros, D. (2009). Long-term effect of continuous positive airway pressure therapy on inflammation markers of patients with obstructive sleep apnea syndrome. Sleep, 32(4):537-543. http://www.citeulike.org/user/HEIRS/article/7756944
Lam, J. C. M. and Ip, M. S. M. Obstructive sleep apnea and the metabolic syndrome: Osa and insulin resistance. Medscape Today. http://www.citeulike.org/user/HEIRS/article/7765845
Gaurdiola, J., Matheson, P., Cavijo, L., Wilson, M., and Fletcher, E. (2001). Hypercoagulability in patients with obstructive sleep apnea. Sleep Medicine, 2(6):517-523. http://www.citeulike.org/user/HEIRS/article/7790684
Nichols, Denise. Original Hypercoagulation Study on Gulf War Veterans. (August 20, 2010) Veterans Today. http://www.veteranstoday.com/2010/08/20/original-hypercoagulation-study-on-gulf-war-veterans/
Salvador, Lourdes. CPAP Machine Improves Gulf War Illness Symptoms for Some. American Chronicle. http://www.americanchronicle.com/articles/view/180225
Espada, S., Rojo, A. I., Salinas, M., and Cuadrado, A. (2009). The muscarinic m1 receptor activates nrf2 through a signaling cascade that involves protein kinase c and inhibition of gsk-3beta: connecting neurotransmission with neuroprotection. Journal of Neural Chemistry, 110(3):1107-1119. http://www.citeulike.org/user/HEIRS/article/7791380
Mauck, B., Lucot, J. B., Paton, S., and Grubbs, R. D. (2010). Cholinesterase inhibitors and stress: Effects on brain muscarinic receptor density in mice. Neurotoxicology. http://www.citeulike.org/user/HEIRS/article/7395495
Beurel, E. and Jope, R. S. (2010). Glycogen synthase kinase-3 regulates inflammatory tolerance in astrocytes. Neuroscience. http://www.citeulike.org/user/HEIRS/article/7264009
Jensen, B., Leeman, R., Schlezinger, J., and Sherr, D. (2003). Aryl hydrocarbon receptor (ahr) agonists suppress interleukin-6 expression by bone marrow stromal cells: an immunotoxicology study. Environmental Health: A Global Access Science Source, 2(1):16+. http://www.citeulike.org/user/HEIRS/article/3802484?show_msg=already_posted
Chan, W. K., Yao, G., Gu, Y.-Z., and Bradfiel, C. A. (1999). Cross-talk between the aryl hydrocarbon receptor and hypoxia inducible factor signaling pathways. The Journal of Biological Chemistry, 274(17). http://www.citeulike.org/user/HEIRS/article/7795717
Foster, G. E., Hanly, P. J., Ostrowski, M., and Poulin, M. J. (2007). Effects of cpap on cerebral vascular response to hypoxia in obstructive sleep apnea patients. Respiratory and Critical Care Medicine, 175(7):720-725. http://www.citeulike.org/user/HEIRS/article/7795723
Matson, C. W., Timme-Laragy, A. R., and Di Giulio, R. T. (2008). Fluoranthene, but not benzo[a]pyrene, interacts with hypoxia resulting in pericardial effusion and lordosis in developing zebrafish. Chemosphere, 74(1):149-154. http://www.citeulike.org/user/HEIRS/article/7795748
Neff, Jerry. Bioaccumulation in marine organisms: effect of contaminants from oil well produced water. 2004. Pg 241. http://books.google.com/books?id=ABIQ_FGKOZcC&lpg=PA241&ots=v-kRmNZQY5&dq=polyaromatic%20hydrocarbons%2Bhypoxia&pg=PA241#v=onepage&q&f=false
Li, Y. J. J., Takizawa, H., Azuma, A., Kohyama, T., Yamauchi, Y., Takahashi, S., Yamamoto, M., Kawada, T., Kudoh, S., and Sugawara, I. (2010). Nrf2 is closely related to allergic airway inflammatory responses induced by low-dose diesel exhaust particles in mice. Clinical immunology (Orlando, Fla.). http://www.citeulike.org/user/HEIRS/article/7730119?show_msg=already_posted
Hsu, H.-F. F., Tsou, T.-C. C., Chao, H.-R. R., Kuo, Y.-T. T., Tsai, F.-Y. Y., and Yeh, S.-C. C. (2010). Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on adipogenic differentiation and insulin-induced glucose uptake in 3t3-l1 cells. Journal of hazardous materials, 182(1-3):649-655. http://www.citeulike.org/user/HEIRS/article/7383158?show_msg=already_posted
Wahl, M., Guenther, R., Yang, L., Bergman, A., Straehle, U., Strack, S., and Weiss, C. (2010). Polybrominated diphenyl ethers and arylhydrocarbon receptor agonists: Different toxicity and target gene expression. Toxicology letters, 198(2):119-126. http://www.citeulike.org/user/HEIRS/article/7408849
Mezrich, J. D., Fechner, J. H., Zhang, X., Johnson, B. P., Burlingham, W. J., and Bradfield, C. A. (2010). An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory t cells. Journal of immunology (Baltimore, Md. : 1950), 185(6):3190-3198. http://www.citeulike.org/user/HEIRS/article/7795863
Ho, P. P. and Steinman, L. (2008). The aryl hydrocarbon receptor: a regulator of th17 and treg cell development in disease. Cell Research, 18(6):605-608. http://www.citeulike.org/user/HEIRS/article/3709745

Melatonin protects against endosulfan-induced oxidative tissue damage in rats.

"Omurtag, G. Z., Tozan, A., Sehirli, A. O. O., and Sener, G. (2008). Melatonin protects against endosulfan-induced oxidative tissue damage in rats. Journal of pineal research, 44(4):432-438."

Read more: CiteULike: Melatonin protects against endosulfan-induced oxidative tissue damage in rats.:

Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression.

"Jager, J., Grémeaux, T., Cormont, M., Le Marchand-Brustel, Y., and Tanti, J.-F. F. (2007). Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology, 148(1):241-251."

Read more: CiteULike: Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression.:

PFOS Significantly Elevates Inflammatory Cytokines From LPS Stimulation.

CiteULike: Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice.: "Dong, G.-H. H., Zhang, Y.-H. H., Zheng, L., Liang, Z.-F. F., Jin, Y.-H. H., and He, Q.-C. C. (2010). Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male c57bl/6 mice. Environmental toxicology."

Neuroprotective and Anti-inflammatory Activities of Ketogenic Diet on MPTP-induced Neurotoxicity.

Comments: I believe the results of this study are indicative of the fact that a keen understanding of the patients environmental illness and the factors that lead to it are crucial for the best holistic treatment and management of it. It is obvious that a one size fits treatment plan is probably not in the best interest of most patients.

"The change of dopamine was very similar to dopaminergic neurons in the SN. KD inhibited the activation of microglia induced by MPTP in the SN. The levels of proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) in the SN were also decreased and induced by MPTP. So, we concluded that KD was neuroprotective and anti-inflammatory against MPTP-neurotoxicity."

Read more: CiteULike: Neuroprotective and Anti-inflammatory Activities of Ketogenic Diet on MPTP-induced Neurotoxicity.:

Methylation-Dependent Gene Silencing Induced by Interleukin 1beta via Nitric Oxide Production

CiteULike: Methylation-Dependent Gene Silencing Induced by Interleukin 1beta via Nitric Oxide Production: "Hmadcha, A., Bedoya, F. J., Sobrino, F., and Pintado, E. (1999). Methylation-dependent gene silencing induced by interleukin 1beta via nitric oxide production. J. Exp. Med., 190(11):1595-1604."

Inflammation and Alterations in Fat Cells By Pesticide Alterations of Anti-inflammatory Protein Genes!

Background: Some experts believe that changes in gene expression may be a consequence of certain chemical exposures. Researchers are now focusing a lot of attention on the effects of these exposures on adipocytes which can produce inflammatory chemokines which may generate inflammation.  It has been observed that some types of exposures are associated with obesity which is a risk factor for diabetes while, others can lead to weight reduction.   Arsenescu demonstrated toxic exposures can stimulate and increase expansion of adipose tissue and other studies show alterations in the process of differentiation of preadipoctyes into adipocytes. In 2008, a preliminary study suggested endothelial dysfunction contributes to fat cell development because adipose stromal cells are in close contact with endothelial cells of capillaries and small blood vessels. (ScienceDaily) Long-term high serum levels of dioxin has been shown to contribute to endothelial dysfunction which provides a possible mechanism for the association of certain exposures to endothelial dysfunction, obesity and a higher risk for diabetes. (Peclova)

In the past, obesity has been characterized by differentiation of preadipocytes to adipocytes and involves the coordinated responses of a number of proteins with fatty acids that leads to increases of the size of fat cells.(Uto-Kondo) However, a recent study suggests that in in the case of abdominal obesity which may have more severe long-term health effects, there is impairment of the ability for preadipocytes to differentiate into adipocytes. Irakson says that "inhibition of this type can lead to a proinflammatory state and macrophage-like phenotype and as Hou explains "elevated levels of TNF-a or Il-1b in inflammatory tissues prolongs the survival of these immune cells and lengthens the durations they remain in an inflammatory state." 

 In one study, eldrin causes inhibition of a binding protein and interfered with expression of the anti-inflammatory protein PPAR-gamma and altered the expression of NF-kappaB which usually decreases as adipocytes differentiate. (Moreno-Aliego) We have suggested that the aberrant signaling from the AhR, which normally is important for cellular homeostasis and contributes to detoxification of PAHs and HAHS, may be an important factor in MCS. Hanlon et el notes that activation of the AhR by dioxin blocks hormone-induced adipocyte differentiation through the suppression of PPAR-gamma. The presence of inflammatory mediators are also associated with insulin resistance which can further impair normal cell function and reductions in the expression of Nrf2 may further complicate it. Chronic inflammation have been suggested as a causal factor in environmental illnesses including obesity and diabetes. One study shows proteins associated with cell death are less efficient in diffentiated adipocytes than in undifferentiated cells when introduced to a reactive species stimulus. Kojima confirmed an increase in antioxidants including MnSOD, catalase, Cu/ZnSOD as well as, FOXO with the the progression of adipocyte differentiation.  From this study, it has been concluded that ROS-generated apoptosis is associated with the expression of FOXO3a in undifferentiated adipocytes and FOXO expression suppresses ROS-apoptosis through activation of scavenging enzymes in differentiated ones. With this study in mind and considering that uncontrolled production of ROS contribute to cellular processes that cause inflammation, preventing differentiation of adipocytes may have negative consequences in certain cases.

Kojima, T., Norose, T., Tsuchiya, K., and Sakamoto, K. Mouse 3t3-l1 cells acquire resistance against oxidative stress as the adipocytes differentiate via the transcription factor foxo. Apoptosis. http://www.citeulike.org/user/HEIRS/article/5998696
Isakson, P., Hammarstedt, A., Gustafson, B., and Smith, U. (2009). Impaired preadipocyte differentiation in human abdominal obesity. Diabetes, 58(7):1550-1557. http://www.citeulike.org/user/HEIRS/article/5017576
Hou, F. F., Boyce, J., Zhang, Y., and Owen, W. F. (2000). Phenotypic and functional characteristics of macrophage-like cells differentiated in pro-inflammatory cytokine-containing cultures. Immunology and cell biology, 78(3):205-213. http://www.citeulike.org/user/HEIRS/article/5998701
Hanlon, P. (2003). Ahr- and erk-dependent pathways function synergistically to mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin suppression of peroxisome proliferator-activated receptor-γ1 expression and subsequent adipocyte differentiation. Toxicology and Applied Pharmacology, 189(1):11-27. http://www.citeulike.org/user/HEIRS/article/5778106
Moreno-Aliaga, M. J. and Matsumura, F. (1999). Endrin inhibits adipocyte differentiation by selectively altering expression pattern of ccaat/enhancer binding protein-alpha in 3t3-l1 cells. Mol Pharmacol, 56(1):91-101. http://www.citeulike.org/user/HEIRS/article/5998840
Uto-Kondo, H., Ohmori, R., Kiyose, C., Kishimoto, Y., Saito, H., Igarashi, O., and Kondo, K. (2009). Tocotrienol suppresses adipocyte differentiation and akt phosphorylation in 3t3-l1 preadipocytes. J. Nutr., 139(1):51-57. http://www.citeulike.org/user/HEIRS/article/5998926
Healthy Blood Vessels May Prevent Fat Growth. ScienceDaily. September 23, 2008.
Pelclová, D., Prázny, M., Skrha, J., Fenclová, Z., Kalousová, M., Urban, P., Navrátil, T., Senholdová, Z., and Smerhovsky, Z. (2007). 2,3,7,8-tcdd exposure, endothelial dysfunction and impaired microvascular reactivity. Human & experimental toxicology, 26(9):705-713. http://www.citeulike.org/group/7254/article/6000451

Estrogen May Make Women Prone To Autoimmune-type Il-1b Inflammatory Conditions

Title: Alternatively activated macrophages in infection and autoimmunity.

Summary: "Women may be at an increased risk of M2-mediated infection and autoimmunity due to estrogen's ability to increase Th2 responses."

Citation: Fairweather, D. and Cihakova, D. (2009). Alternatively activated macrophages in infection and autoimmunity. Journal of autoimmunity. http://www.citeulike.org/user/HEIRS/article/5948117

Nuerotoxicity, Noradrenaline and Il-1

Title:

Summary: "In parallel with its ability to increase IL-1ra and IL-1RII, noradrenaline prevented neurotoxicity in cortical primary neurons induced by conditioned medium from IL-1beta treated mixed glial cells. These data indicate that noradrenaline negatively regulates IL-1 system in glial cells and has neuroprotective properties in situations where IL-1 contributes to pathology."

Citation: McNamee, E. N., Ryan, K. M., Kilroy, D., and Connor, T. J. (2009). Noradrenaline induces il-1ra and il-1 type ii receptor expressions in primary glial cells and protects against il-1beta-induced neurotoxicity. European journal of pharmacology. http://www.citeulike.org/user/HEIRS/article/5923308

Infection/Endotoxin in Chronic Fatigue, Fibromyalgia and Multiple Chemical Sensitivity.

Definition: Endotoxin: a toxic component of bacteria not excreted by live bacteria but induces the inflammatory cascade and production of NO. (Endotoxin)

 An increasing number of scientific publications support the hypothesis that endotoxin infection and sickness syndrome may be important factors in environmental illnesses including fibromyalgia, chronic fatigue syndrome and quite possibly MCS. In fact, sickness syndrome would be a reasonable and holistic approach for explaining many of the behavioral, physical and emotional complications that are common in environmental illness. Sickness syndrome is described as the presence of a variety of symptoms including malaise, fatigue, sleep disturbances, appetite changes, brain inflammation, mood changes such as anxiety and depression and a host of other symptoms that occur as a reponse to injury or infection.  These responses occur both in humans and animals and some propose it is in part, adapative responses that are generated to alter the responses of the host and their social network. Over the past several years, there has been an significant amount of research on sickness syndrome. The occurence of which can be attributed to inflammatory cytokines that alter neurotransmission and genetic expression. There have been studies that show altered gene expression in environmental illnesses; the consequences of which can be quite severe and unexpected. Il-10 is an anti-inflammatory cytokine that has been shown to modulate the severity of sickness syndrome through interaction with HO-1. HO-1 is also a cytokine that is induced by activation of Nrf2, although there are other pathways that can induce this antioxidant. Recently, it has been demonstrated that the protective effect of an endogenous peptide thryotropin, against the damaging effect on the dopamine system from paraquat, is due to the chemicals ability to activate Nrf2 to reduce reactive species and increase the antioxidant glutathione. Other studies have demonstrated that thyrotropin is able to reverse hyperglycemia by increasing beta cell function and reducing programmed cell death. (Luo) Insulin resistance and diabetes are suspected to be important consequences of the sustained presence of inflammation and inflammatory cyokines that are characteristic of environmental illnesses.

A recent published study showed that there is brain disfunction in multiple chemical sensitivity (Orriols) and last week I suggested that some of the cognitive effects could be from an altered expression of BDNF. Of course, there are any number of factors such as malnutrition and inflammation that can influence cognitive function. Neurotransmitter regulate and can alter cognition and are modulated by factors that produce "sickness syndrome".  According to the author of the recent MCS study, SPECT scans showed alterations in the regions of the brain including the cingulus, striatum and the hippocampus in addition to others. Pekary et al explains that a common environmental toxin LPS has the potential to alter the expression of thyrotropin which may have an impact on LPS toxicity. The study showed elevations of cytokines and corticosterone after LPS with a transient drop in T3. Other results showed a decrease in thyrotropin-releasing hormone in certain areas of the brain while increasing it in others. Thyrotropin has been shown to improve recovery after neurological dysfunctions such as brain trauma and epilepsy in humans and animals and be neuroprotective against NMDA neurotoxicity. (Pizzi) These regions the author noted are areas that are associated with the neuroimmunomodulatory effects of sickness and injury and danger and appear to be similar to those effected in MCS SPECT scans. Also, a sustained elevation in TRH was present in b-cells accompanied by LPS-impaired insulin secretion. From these findings, the author concluded that thyrotropins can mediate and moderate the behavioral and toxic effects of LPS. In addition, LPS elevates inflammatory cytokines including Tnf-a, Il-6 and Il-1b and also increases expression of TLR receptors 2 and 4 and causes a prolonged sickness behavior in aged animals. Taking these findings into account and the fact that thryotropin mediate their positive effects through Nrf2, then one can assume that alterations in the antioxidant system may exacerbate the toxic effects generated by LPS endotoxin  It is also important to mention that Nrf2 levels drop as a consequence of the aging process(Godbout). This could lead one to propose that Nrf2 alterations from aging and other impairments and LPS may at least in part, mediate the effects in MCS. There has been evidence that hyperglycemia (which can be reversed with thyrotropin) sensitizes TRPV1 receptors which is implicated in MCS (Pall) and diabetes complications and TRPV1 may have direct or indirect effect on the release of neurotransmitters. (Pabbidi) Neuropeptides releases from capsaicin-sensitive efferents provide a protective mechanism against LPS but also increase bronchoconstriction which can increase airway hyperresponse. (Elekes) From these results and other studies, I have suggested that insulin resistance and hyperglycemia from chemical exposures may contribute to some of the inflammatory responses in MCS.

Endotoxin or LPS has been implicated as a possible pathway to the development of chronic fatigue syndrome. Above we noted that LPS increases the expression of toll-like receptors 2 and 4. Toll receptors recognize certain components on bacteria and transduces bacterial invasion through this recognition and has important relevance in preventing infection (Light) and expressed on a variety of cells including dendritic cells, B cells, neutraphils and macrophages. Defects in TLR expression can lead to an increase in susceptibility to infection from a number of pathogens while aberrant signaling of TLR such as from LPS are implicated in causing sepsis or even inflammatory or autoimmune-type conditions. (Harding) Activation of TLRs can lead to initiation of the the inflammatory pathway NF-kappaB and LPS endotoxins are ligand of TL4. Interestingly, saturated fats (bad fat) can induce inflammatory markers through TLR4 and therefore, saturated fats can alter gene expression through TLR4 interaction. For instance, the main component of coconut oil, lauric acid, has been demonstrated to potentiate the inflammatory effects of LPS COX-2. (Lee)  The just published Light study on chronic fatigue syndrome shows an increase in TLR4 after exercise and Light suggests this is due to "lesser fitness" in CFS patients. Light goes on to further explain that Il-10 is upregulated in CFS patients after exercise and one of its roles is to inhibit the production of Tnf-a which is also consistent with recent reports of an anti-inflammatory profile in FM. This and other studies of CFS revealed symptom flares may be related to cytokine activity postexercise. Notably, Tnf-a was elevated in muscle and Light explains that fatigue and muscle pain in CFS might be from the enhanced activation of "fatigue" and "nociceptive" afferents supplying muscle. Other supporting evidence of muscle involvement included elevations of ASIC3 channels that are often increased by muscle and joint inflammation. The elevation of Il-10 in the Light study was correlated to those patients with prolonged fatigue and pain but who also had elevations in pro-inflammatory cytokines and evidence of overall enhanced immune response. LPS has been shown to have a close relationship with sensory nerves and TLR4 receptors have been found on sensory nerves. The interaction between LPS and TLR4 may enhance the complications of TRPV1 activation. (Clark) In addition, Suter demonstrated that TLR2 and TLR4 are necessary for nerve-induced microglia activation and pain sensitization. (Suter)The presence of nociceptors on trigeminal nerves that suggests they recognize bacterial products and contribute to pain during infection. (Ball)

Citations and Original Document

Multiple Chemical Sensitivity, Altered Brain Responses and Ups and Downs Of BDNF

 Multiple Chemical Sensitivity, Altered Brain Responses

and Up and Down Regulation of Proteins

 

Multiple chemical sensitivity is characterized by a heightened physical and emotional sensitivity to "agents" such as fragrance and chemicals in the environment.  A recent study that was posted on The Canary Report documents new research that supports the fact that MCS has neurogenic origins. While the idea is not new, this study provides SPECT imaging results that show abnormalities in MCS patients.  According to the author, the findings show neurocognitive impairment and disfunction in the areas of odor-processing. (Orriols) A past study showed similar alterations in odor processing without neural sensitization and suggests MCS hypersensitivity is a result of alterations in the top-down regulation of the odor-response. (Hillert) I suggest that some of the effects of MCS may be a consequence of alterations in the production of BDNF which plays a role in the regulation of olfactory bulb neurogenesis.
 

In past blogs, we have mentioned a neuropeptide brain-derived neutrophic factor. BDNF is important for long-term survival of neurons including those involved with learning and memory and control of downstream targets including neurotransmitters such as dopamine and glutamate. (Paredes) It also is important for olfactory neurogenesis and fine odor discrimination and function and its functions suggests critical importance for detecting and processing of changes in the environment, ie. odors. (Yuan) In recent years, research had identified certain functions of BDNF although there is still much to be learned. These findings include important roles in glucose and cognitive function regulation. More importantly it increases NAD+ levels which would suggests it elevates SIRT1 and protects against excitoxicity. (Liu) SIRT1 is an important regulating protein that upregulates regulatory proteins and acts through PGC-1a which is necessary for  mitochondrial biogenesis. In addition, it interacts with Nrf2 and other proteins to maintain cellular homeostasis. One study showed women with impaired insulin function such as insulin resistance and diabetes had lower BDNF levels than controls. Women with higher BDNF has poorer explicit memory and this suggests higher levels of BDNF may not always be indicative of good health but is probably a mechanism to respond to damage. (Arentoft) Markham shows that neutrophins like BDNF can not only modify neuronal plasticity but also modifies brain metabolism and increases mitochondrial function which can have both positive and negative tissue-specific effects.

 

Parkinson's disease is neurodegenerative condition that has been linked to environmental toxin exposure and in one study it was demonstrated that carnosis acid (CA) in rosemary can reduce the down-regulation of BDNF from the pesticide dieldrin which is no longer used but may be present in the environment and tissue because it is bioaccumulative.  This author explains that CA "safeguards dopaminergic neuronal cells from environmental neurotoxins by enhancing brain-derived neurotrophic factor and repressing apoptotic molecules."  Many have noted that pesticides can mediate the development of MCS and alteractions in gene regulation, such as BDNF, provides one explanation of why these exposures have a long-term impact on cognitive function. (Park) This study demonstrates that BDNF protects dopamine cells and might suggest  lower levels of BDNF may produce aberrant behaviors controlled by dopamine including changes in mood and addictive behavior. A just published study has also implicated a decrease in glutaminergic neurotransmission may also be a factor in learning and memory deficits from dieldrin.  Other environmental factors such as high-fat diets significantly reduces BDNF levels enough to alter cognitive function regulation and aggravates effects of brain injury. (Wu) One author is quoted as saying, "when you have adquate levels of BDNF, then memories do not come back to haunt you...which
seems reminiscent of the more behavior-influencing effects of PTSD.
 

In addition, it has been demonstrated the stress response including the secretion of cortisone has an impact on the production of BDNF and if stress persists for too long this can lead to atrophy of the hippocampus. Zhou proposes cortisone inhibits long-term potentiation. This, he says, is mediated by a presynaptic mechanism and this mechanism may involve the decrease in BDNF expression. BDNF has been implicated as a factor in a number of mental health conditions including depression and schizophrenia. Behavioral factors such as exercise, calorie restriction and antidepressants increase levels of BDNF and as numerous studies have demonstrated, these factors can also reduce mental health symptoms including those for depression. (Daney)
 

For several years, researchers have studied drugs in a class of AMPAkines for treating a variety of conditions such as schizophrenia, problems with attention span and alertness and memory problems associated with dementia and Alzheimer's. Interestingly, this class of drugs also significantly elevate BDNF and also LTP which is an indicator for memory formation. (Daney) Alterations in BDNF levels have been associated with fear-induced olfactory learning which suggests a possible connection to MCS and the behavioral changes that may occur when a person with MCS is confronted with an offending "odor". However, Jones argues that a stressor and odor exposure must occur together for fear-induced olfactory learning and one might suggest that the stressor may come from the immune response itself. In any case, it again provides proof that BDNF influences the olfactory system and very well could intensify the behavioral aspects of MCS.  In other blogs, I have mentioned odors activate the TRP receptors and consistent and long-term activation can lead to endoplasmic reticulum stress, cellular dysfunction and possible alterations of the "adaptive pathway" Nrf2 through PERK and subsequently negatively impact subsequent immune responses to offensive and hazardous stimuli. Activation of Nrf2 can be dependant or independant of oxidative stress. (Ho)      
 

Imbalances in cellular homeostasis can lead to overexpression of BDNF and pain generation. Norman explains neuropathic pain and depression are often co-morbid and demonstrated how nerve injury produces inflammation resulting in both allodynia and depression-like symptoms and Il-1b. (This of course sounds a lot like sickness syndrome even though the author does not mention it.) The study also demonstrated that chronic stress exacerbated the levels of neuropathic pain, depression, Il-1b and elevated BDNF levels may be compensatory like it was suggested in the paragraph above. Application of a corticosteroid inhibitor prevented the effects of the stress and an inhibitor of Il-1 prevented the depression and the neuropathic pain. (Norman)

Numerous studies have suggested environmental illnesses may be due to the dysregulation of insulin and glucose homeostasis on specific receptors that regulate inflammation and cellular function and it is my belief this is true of MCS.  Several studies have shown that cyokines can influence the regulation of gene expression and there is no reason this is not also true of MCS. As the author suggests, MCS may be the result of abnormal odor processing after chemical exposure and the effects include cognitive impairments. TRPV1 has been implicated as an important factor in the development of MCS (Pall) and also in neuropathic pain (Wipedia) and recently, it has been demonstrated altered TRPV1 function may play a role in diabetes. (Pabiddi) BDNF have been shown to be elevated in fibromyalgia and as Martin-Lavin explains it has been suggested fibromyalgia is in part, neuropathic pain and suspected to be a consequence of abnormal summation of pain and spinal-cord reflexes. (Martinez-Lavin) Other studies have demonstrated that insulin and IGF-1 potentiates the activity of TRPV1 through PKC (Van Burnen)  and several reports suggest chemical exposure causes inflammatory responses that induce insulin resistance and hyperglycemia which can impair mitochondrial function. In addition, a growing body of evidence links obesity and diabetes and the "removal" of TRPV1 fibers improve pain decreases weight gain and improves glucose tolerance both in high-fat diets and diabetic models. As we have noted, chemical bioaccumulation mimic the effects and are exacerbated by high-fat diet models and therefore, these findings are of importance to studies of the impact toxic injury on metabolism.  Experiments changing TRPV1 function prevents pancreatic beta cell destruction and autoimmune diabetes and (Suri) hyperglycemia can elevate reactive species which activates TRPV1 expression and at higher levels cause cell death. Earlier we mentioned that insulin function can regulate BDNF and alterations in levels are associated with insulin resistance and diabetes. Exercise increases levels of BDNF but excess energy production from exercise or a high-calorie diet can increase ROS and cause cellular overload and reductions in BDNF and cognitive function. (Go'mez-Pinilla) Recent findings have shown that both BDNF and GDNF (another neural factor) can regulate the expression of TRPV1 and TRPA1 (in a slightly different manner) leading to enhanced neuronal sensitivity to stimuli and elevations in other receptors.  (Ciobanu)

 

Next Research Blog:

• What the Light Study on Chronic Fatigue Syndrome Says and What It Does Not Say!

Library Resources:

• BDNF

Citations and References:

 

Inflammatory Proteins and IL-10 in Obesity and Pathogenic Exposure: Implications for Sickness Syndrome and Fatigue!

Background: Sickness syndrome is a response to infection and inflammation and has been associated with production of Il-1b. Fatigue is a common symptom in environmental illness and may be a factor in sickness syndrome and recent studies provide evidence that activation of the Il-1 system may be a factor in causing the fatigue. Other studies demonstrate that Il-10 can modulate the severity of sickness syndrome through its interactions with HO-1 and other proteins such as BDNF.(Richwine) Richwine has also demonstrated that inflammatory processes increase in aged mice compared to adults. Meador has explained that IL-10 is associated with lower levels of inflammatory cytokines including Tnf-a, Il-1 and Il-6 in muscle and non-muscle.  The effects of aging on the expression of Il-10 would suggest alteration in SIRT1 or Nrf2/HO-1 and/or changes in expression of another gene that is effected by the aging process and high-fat diets.

New Research:
Title: Environmental and genetic factors influence the relationship between circulating Il-10 and obesity phenotypes.

Summary: "circulating IL-10 levels were associated not only with obesity status but also with genetic factors and with the exposure to environmental pathogens."

Citation: Bassols, J., Botas, P., Moreno-Navarrete, J. M., Delgado, E., Ortega, F., Ricart, W., and Fernandez-Real, J. M. (2009). Environmental and genetic factors influence the relationship between circulating il-10 and obesity phenotypes. Obesity (Silver Spring, Md.). http://www.citeulike.org/group/7167/article/5898650

Related Posts:

• Chronic Fatigue, Insulin Resistance, Il-10 and Sickness Syndrome
• CFS, Probiotics and Il-10
• Sickness Syndrome, CFS, Fibromyalgia, IL-10 and HO-1

Additional References:
Richwine, A. F., Sparkman, N. L., Dilger, R. N., Buchanan, J. B., and Johnson, R. W. (2009). Cognitive deficits in interleukin-10-deficient mice after peripheral injection of lipopolysaccharide. Brain, behavior, and immunity, 23(6):794-802. http://www.citeulike.org/user/HEIRS/article/4710107
Godbout, J. P., Chen, J., Abraham, J., Richwine, A. F., Berg, B. M., Kelley, K. W., and Johnson, R. W. (2005). Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. The FASEB Journal, 19. http://www.citeulike.org/user/HEIRS/article/4745254
Meador, B. M., Krzyszton, C. P., Johnson, R. W., and Huey, K. A. (2008). Effects of il-10 and age on il-6, il-1beta, and tnf-alpha responses in mouse skeletal and cardiac muscle to an acute inflammatory insult. Journal of applied physiology (Bethesda, Md. : 1985), 104(4):991-997. http://www.citeulike.org/user/HEIRS/article/5488212

Il-1b Alters Neurotransmitter Responses- Implications for Intestinal Inflammation!

Title: Prolonged il-1β exposure alters neurotransmitter and electrically induced ca²⁺ responses in the myenteric plexus.

Summary: This study suggests that "IL-1b could be implicated in the motility disturbances observed during gastrointestinal inflammation."


Kindt, den Berghe, Boesmans, Roosen, and Tack (2009). Prolonged il-1β exposure alters neurotransmitter and electrically induced ca²⁺ responses in the myenteric plexus. Neurogastroenterology & Motility, 9999(9999).