ABSTRACT
While the key initiating processes that trigger human autoimmune diseases remain enigmatic, increasing evidences support the concept that microbial stimuli are among major environmental factors eliciting autoimmune diseases in genetically susceptible individuals. Here, we present an overview of evidences obtained through various experimental models of autoimmunity for the role of microbial stimuli in disease development. Disease onset and severity have been compared in numerous models under conventional, specific-pathogen-free and germ-free conditions. The results of these experiments suggest that there is no uniform scheme that could describe the role played by infectious agents in the experimental models of autoimmunity. While some models are dependent, others prove to be completely independent of microbial stimuli. In line with the threshold hypothesis of autoimmune diseases, highly relevant genetic factors or microbial stimuli induce autoimmunity on their own, without requiring further factors. Importantly, recent evidences show that colonization of germ-free animals with certain members of the commensal flora [such as segmented filamentous bacteria (SFB)] may lead to autoimmunity. These data drive attention to the importance of the complex composition of gut flora in maintaining immune homeostasis. The intriguing observation obtained in autoimmune animal models that parasites often confer protection against autoimmune disease development may suggest new therapeutic perspectives of infectious agents in autoimmunity.
ABSTRACT
Interleukin-6, a multifunctional cytokine upon binding to its receptor on hepatocytes regulates production of acute phase proteins involved in local and systemic inflammation. Gene expression and biosynthesis of IL-6 and its receptor (IL-6 R/gp130) is under complex regulation. Histamine, in addition to its principal role in immediate type hypersensitivity has been described to modulate IL-6 production and expression of IL-6 receptor. In this study, the IL-6 and IL-6 receptor expression was examined in histamine deficient histidine decarboxylase (HDC) knock-out mouse model. Our data suggest that in histamine deficient mice the inducibility of IL-6 is significantly reduced, whilst more IL-6 receptor/gp130 mRNA expresses in the liver than in wild type (HDC(+/+)) mice. These in vivo findings confirm earlier in vitro results and emphasize the efficacy of antihistamines in local IL-6 related processes.
