Relevance of the cytokine-HPA axis loop during autoimmunity

Journal/Book: Z Rheumatol 1999; 58: 298. 1999;

Abstract: A. del Rey; Institut für Normale und Pathologische Physiologie -Immunophysiologie- der Philipps-Universität Marburg Probably one of the best established models of autoimmunity in which it has been shown that increased endogenous levels of glucocorticoids play an essential role for survival is experimental autoimmune encephalomyelitis (EAE). Lewis rats in which EAE is induced by subcutaneous injection of guinea-pig myelin basic protein (MBP) manifest a single episode of paralysis from which they recover spontaneously. Th1 lymphocytes mediate the autoimmune component of the disease and cytokines such as interleukin-1ß (IL-1ß) and tumor necrosis factor a (TNFa) are implicated in the pathogenesis of EAE. The levels of glucocorticoids in blood increase during the disease. This stimulation of the pituitary-adrenal axis is essential for the recovery from EAE since adrenalectomy results in death of the animals. In spite of the crucial role played by the increased glucocorticoid output in the recovery from EAE the mechanism that triggers this endocrine response is not known. It is reasonable to assume that the HPA axis is stimulated by the stress caused by the paralytic attack that characterizes this disease. Alternatively such an increase in blood glucocorticoid levels could be at least in part immunologically mediated since it has been previously shown that the immune response to innocuous antigens results in stimulation of the HPA axis. On this basis we have investigated the possibility that an immunoregulatory circuit involving immune-derived products and glucocorticoid hormones operates during the course of EAE. Using chronically cannulated rats we have observed that the increase in corticosterone levels in Lewis rats which received MBP precedes the appearance of the clinical signs. We have also found that endogenous glucocorticoid levels are increased following injection of MBP into PVG rats. ... le

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