The cytokine-HPA axis circuit contributes to prevent or moderate autoimmune processes.
There is evidence that an immunoregulatory circuit integrated by immune-derived cytokines and the hypothalamus-pituitary-adrenal (HPA) axis operates during certain pathological conditions. For example, it has been shown that IL-1 is the main mediator of the increase in ACTH and corticosterone blood levels detected in models of viral infection and bacterial endotoxins. This endocrine response has protective effects during septic shock. In experimental models of tumors, there are also clear indications that the increase in glucocorticoid levels detected during the growth of a lymphoma is mediated by immune-derived products and contributes to the inhibition of the inflammatory response. The disruption of the cytokine-HPA axis circuit can predispose to autoimmunity. This has been shown in animal models of spontaneous autoimmune thyroiditis, lupus-like disease, and experimental arthritis. More recently, it has been shown that the proper operation of this circuit contributes to preventing or moderating autoimmunity. The recovery of animals from experimental autoimmune encephalomyelitis (EAE) is clearly dependent on an increase in endogenous glucocorticoid levels. It has been recently shown that this endocrine response is, at least in part, triggered by the immune response to the encephalitogenic antigen and mediated by the endogenous IL-1 produced during the disease. These examples support the concept that the cytokine-HPA circuit plays a protective role during certain pathologies and that its disruption can lead to predisposition to or aggravation of autoimmune diseases.
del Rey
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A
Institute of Physiology, Div. of Immunophysiology, Philipps-University, Deutschhausstr. 2, 35037 Marburg, Germany.
Besedovsky
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HO
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007108:Immune Tolerance / Q000276:immunology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*
D016207:Cytokines; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone