DIFFERENT ROLES OF BRAIN INTERLEUKIN-1 IN THE ADRENOCORTICOTROPIN RESPONSE TO CENTRAL VERSUS PERIPHERAL ADMINISTRATION OF LIPOPOLYSACCHARIDE IN THE RAT

Although it is web established that peripheral administration of endot oxin activates the hypothalamic-pituitary-adrenal (HPA) axis, informat ion is very limited regarding whether central administration of endoto xin can similarly stimulate the endocrine axis. Moreover, it is also u nknown whether a difference exists in the mode of involvement of brain -derived cytokines in determining the HPA response to peripheral vs ce ntral administration of endotoxin. In the present study, the authors a ttempted to gain more knowledge on these issues focusing on interleuki n (IL) 1 in the brain, one of key pro-inflammatory cytokines mediating the immune-endocrine network. In male rats, both intravenous (i.v., 1 00 mu g/kg body weight) and intracerebroventricular [i.c.v. (the 3rd v entricle), 10 mu g] injections of Escherichia coli lipopolysaccharide (LPS) caused a significant elevation of adrenocorticotropin (ACTH) lev els in plasma, even though peaked ACTH responses occurred earlier afte r the i.v. (60 min post-injection) than the i.c.v. (120 min post-injec tion) LPS. Although the ACTH response to i.c.v. LPS was significantly suppressed by a prior (5 min) i.c.v. administration of IL-1 receptor a ntagonist (IL-1Ra, 1 mu g), the hormonal response to i.v. LPS was not. That this dose of IL-1Ra was not biologically a small dose was indica ted by another experiment that the same dose of i.c.v. IL-1Ra was able to significantly suppress the ACTH response to an i.c.v. injection of recombinant human IL-1 beta (50 ng). These results suggest that i.c.v . LPS, as i.v. LPS, can stimulate ACTH secretion in the rat, and this hormonal response may, at least in part, be mediated by brain-derived IL-1. Although there is one previous study reporting an important role of central IL-1 in mediating the HPA response to systemic LPS treatme nt, our present data suggest that such a mechanism may not operate bef ore and during an early, peak phase of ACTH secretion after i.v. LPS. (C) 1998 Academic Press Limited.