This article is not intended to be healthcare or medical advice. Before starting any health or medical related regimen seek advice from your Primary Care Physician or an M.D.
IL-10 has a hand in many important things, many of which appear to be related to different chronic illnesses. Similarly, the ARH (Aryl Hydrocarbon Receptor), modulates many immune related functions, pathways, and genes. A summary is noted directly below, with details forthcoming later on. For now, this is a work in progress.
IL-10 Summary:
Master regulator of the innate immune system
Inhibits the pro inflammatory cytokine TNF-alpha and IL-6
Regulates the gene CPOX, in the heme biosynthesis pathway. Heme and the gene HMOX1 regulate mast cells.
IL-10 is inhibited by the mycotoxins Citrinin and Gliotoxin[1]
IL-10 increased by the mycotoxin Zearalanone
Certain IL-10 mutations are linked to IBD, Chrone's Disease, and gut wall barrier disruption when exposed to emulsifiers in food and supplements [2, 3]. IL-10 gets elevated with exposure to emulsifiers in the diet, and then can block heme synthesis.
Most authors believe that IL-10 levels are higher in patients with CFS than in healthy controls . A longitudinal study reported increased IL-10 levels accompanied by decreased IFN-γ/IL-10 ratio in patients with CFS during a 1-year observation period. In a longitudinal research, IL-10 was assessed in PBMCs of patients with CFS and in healthy controls; IL-10 levels exhibited a significant increase at baseline, followed by a significant drop at 6 months and finally no significant variation at 12 months. Thus, the role of IL-10 in CFS requires further investigation.[20]
Concentration levels of IL-10 in CFS/ME patients in comparison to controls. IL-10 was the only cytokine significantly decreased in the CSF samples of the CFS/ME patients. The black bars represent data from the CFS/ME patients and the white bars represent data from the control patients. Data is represented as mean ± standard error of the mean (SEM)[21]
The Aryl Hydrocarbon Receptor is a cofactor for IL-10.
Binding of IL-10 to its receptor activates a major JAK1-TYK2-STAT3 signaling cascade, which culminates with the induction of the STAT3-mediated anti-inflammatory response. [25]
AhR regulates IL-10-production in T R 1 cells induced by TGF-β and IL-27 Naïve CD4 + T-cells from IL-10 reporter mice (Vert-X mice) were cultured with IL-27 and TGF-β in the absence (Control: Ctrl) or presence of the AhR agonists FICZ (100nM) or TCDD (100nM) a) IL-10.
When considering the data obtained for the two anti-inflammatory cytokines (IL-10 and IFN-β) detected, it is interesting to note the increases registered in the presence of CMC, with this augmented production being statistically significant (p < 0.05) for IFN-β. This behavior is even more relevant if one considers that IL-10 is associated with the dampening of intestinal inflammation, IBD and ulcerative colitis risk reduction, as this interferon limits the secretion of pro-inflammatory cytokines, deactivates macrophages and inhibits the secretion of Th1-related cytokines.
Aryl Hydrocarbon Receptor
Modulates IL-10; and thus heme - which implies indirect regulation of tryptophan metabolism (think The Metabolic Trap)
Modulates IDO1 directly, and thus directly regulates tryptophan metabolism
Modulates a number of downstream pathways including the JAK-STAT pathway
Two other genes (AHRR) and ARNT (also known as HIF1a - Hypoxia Inducible Factor 1) regulate ARH (Aryl Hydrocarbon Receptor)
Co regulates hypoxia states
Regulates the NMDA Receptors
Regulates IL-6, and NQO1 (ubiquination)
Regulates NADPH Oxidase, and KIT genes and thus mast cells
The aryl hydrocarbon receptor can be activated (and over activated) by specific fruits, vegetables, and herbs. ARH under expressed is problematic, and over expressed is problematic. For some a plant based diet can help express a compromised AHR gene to appropriate levels, while for others, too much stimulation from certain vegetables and fruits causes immune over activation. This could be one plausible explanation why some people benefit immune wise (fatigue) from a carnivore diet, and why some very much benefit from more vegetables and fruits. This article will be a series related to immune modulation, and will be expanded over time.
Similarly, IL-10 is strongly effected by mycotoxins, and intestinal inflammatory conditions. Here we see why both mold and diet can play such a strong role in recover from chronic illness. IL-10 is dysregulated with intestinal inflammatory conditions that vary from emulsifiers, and infections like clostridia difficile. Many studies exist, where modulation of IL-10 and AHR, can help resolve these conditions, mostly in mice studies (see references).
References
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