DISTURBED IMMUNOENDOCRINE COMMUNICATION VIA THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS IN MURINE LUPUS

Immune reactions and mitogen stimulation of mammals and chickens lead to an increase of glucocorticoid (GC) plasma levels concomitant with t he immune response. Interleukin (IL) 1, one of the most important gluc ocorticoid increasing factors produced by cells of the immune system, acts via the hypothalamo-pituitary-adrenal (HPA) axis. This pattern of immunoendocrine feedback communication is altered in autoimmune disea se (AID) and represents a possible site of action for GC therapy. In t he present study we investigated the role and possible underlying mech anisms of a disturbed immunoendocrine communication via the HPA axis i n murine lupus. We analyzed the response to recombinant human (rhu) IL -1 alpha in AID-prone mice [NZB, NZW, (NZB/NZW)F1, MRL/MP-lpr] in comp arison to nonautoimmune, normal control mice (Swiss, C3H/HeJ, MRL/MP-/+) at different levels of the HPA axis. To this end, we quantified th e plasma levels of ACTH, corticosterone, and corticosterone-binding gl obulin (CBG) and determined various pathology parameters for autoimmun ity. AID-prone mice produced nearly the same levels of plasma corticos terone after injection of rhu IL-1 alpha as normal mice, but had basel ine corticosterone levels consistently higher, thus resulting in signi ficantly lower corticosterone increasing ratios. ACTH levels increased after rhu IL-1 alpha injection, but there was no clearcut difference in the increasing ratios of AID-prone and normal strains. CBG levels s howed no difference. As expected, there was a correlation of pathology parameters for autoimmunity and the altered immunomodulatory response to rhu IL-1 alpha per group. On an individual basis, there was no suc h correlation. In conclusion, our results confirm the existence of a d isturbed immunoendocrine communication in AID-prone mice. This disturb ance clearly differs from individual to individual and also among diff erent types of AID. (C) 1996 Academic Press.