Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(lpr) mice

The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the imm une system during immune reactions, causing an elevation of systemic glucoc orticoid levels that contribute to preservation of the immune reactions spe cificities. Previous results from our laboratory had already shown an alter ed immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axi s in autoimmune disease-prone chicken and mouse strains. In the present stu dy, we further investigated the altered glucocorticoid response via the hyp othalamo-pituitary-adrenal axis in murine lupus. We established the circadi an rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocortico tropic hormone and melatonin, as well as the time response curves after inj ection of interleukin-1 of the first three parameters in normal SWISS and l upus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/MP-f as(IPr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, an d plasma corticosterone levels are elevated during the resting phase. Diurn al changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormon e were normal compared to healthy controls. These data indicate that MRL/MP -fas(IPr) mice not only show an altered glucocorticoid response mediated vi a the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our finding s may have implications for intrathymic T cell development and the emergenc e of autoimmune disease. (C) 2000 Academic Press.