Cytokines mediate protective stimulation of glucocorticoid output during autoimmunity: involvement of IL-1.
Endogenous glucocorticoid levels are increased during experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Although this endocrine response is essential for survival, the mechanism that triggers the stimulation of glucocorticoid output during the disease remains unknown. We report here that 1) after immunization with the encephalitogenic antigen myelin basic protein (MBP), increased blood glucocorticoid levels are not only observed in Lewis rats, but also in PVG rats, which do not develop EAE; 2) immune cells obtained from animals with EAE and stimulated in vitro with MBP produced mediators that increased glucocorticoid levels when administered to naive recipients; and 3) acute in vivo blockade of interleukin-1 (IL-1) receptors inhibited, to a large extent, the increase in corticosterone levels during EAE. These results show that the increase in corticosterone levels after immunization with MBP can be dissociated from the stress of the paralytic attack that characterizes EAE. Furthermore, they indicate that an endocrine response, which is decisive for the prevention or moderation of EAE, is mainly the result of the stimulation of the hypothalamic-pituitary-adrenal axis by cytokines produced during the immune response that induces the autoimmune disease.
Division of Immunophysiology, Institute of Physiology, Medical Faculty, D-35037 Marburg, Germany.
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del Rey
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Klusman
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Besedovsky
D000704:Analysis of Variance; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D005620:Freund's Adjuvant; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D053590:Interleukin 1 Receptor Antagonist Protein; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology
D053590:Interleukin 1 Receptor Antagonist Protein; D004676:Myelin Basic Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D005620:Freund's Adjuvant; D003345:Corticosterone