AJP - Endocrinology and Metabolism, Vol 266, Issue 6 E986-E992, Copyright © 1994 by American Physiological Society

ARTICLES

Effect of IL-1 receptor antagonist and antiserum to TNF-alpha on LPS-induced plasma ACTH and corticosterone rise in rats

O. Ebisui, J. Fukata, N. Murakami, H. Kobayashi, H. Segawa, S. Muro, I. Hanaoka, Y. Naito, Y. Masui, Y. Ohmoto and al. et
Department of Medicine, Kyoto University, Faculty of Medicine, Japan.

Using an antiserum against tumor necrosis factor (TNF)-alpha and an interleukin (IL-1) receptor antagonist, we studied putative roles of these cytokines in mediating the endotoxin-induced elevation of plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in freely moving rats. Intravenous administration of Escherichia coli lipopolysaccharide (LPS) increased plasma ACTH and corticosterone levels in a dose-dependent manner. The plasma corticosterone reached to its highest level among a series of experiments after the administration of even the smallest dose (0.03 microgram/kg) tested. Plasma ACTH and corticosterone levels in these rats were completely inhibited by the intravenous administration of anti-murine TNF-alpha-rabbit antiserum (anti-TNFAS) after the administration of LPS but not by the intravenous administration of IL-1 receptor antagonist (IL-1RA). On the other hand, both recombinant human IL-1RA and anti-TNFAS significantly inhibited plasma ACTH increase stimulated with 10 micrograms/kg LPS. These findings indicate that 1) when the plasma corticosterone increase induced by intravenous LPS remains below its maximum, the effect is exclusively mediated by TNF-alpha, and 2) when a larger amount of LPS is administered, both IL-1 beta and TNF-alpha participate at least in part in the hypothalamic-pituitary-adrenal axis activation.

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