A significant role of leukemia inhibitory factor in the brain and periphery in endotoxin stimulation of adrenocorticotropin secretion in the rat

Leukemia inhibitory factor (LIF) is considered as another important cytokin e regulating the activity of the hypothalamo-pituitary-adrenal axis. In thi s: study, we examined the effects of intravenous (iv) and intracerebroventr icular (icv) administrations of anti-LIF antibody on plasma adrenocorticotr opin (ACTH) responses induced by intraperitoneal administration of lipopoly saccharide (LPS, 250 mu g/kg) in male rats. Fifteen minutes before the LPS injection, anti-rat LIF antibody or control serum was given iv or icy. The antibody was administered at two different concentrations, i.e. undiluted a nd five-times diluted. Irrespective of the route of administration, the ant i-LIF antibody partially but significantly suppressed ACTH responses to LPS , and its suppressive effect was similar between its two different concentr ations. These results indicate that the anti-LIF antibody already exerted i ts maximal effects at its diluted preparation, and hence that the role of L IF in LPS-stimulated ACTH secretion is essentially partial. This is the fir st study to demonstrate in vivo that LIF in both the brain and general circ ulation plays a significant role in mediating endotoxin-stimulated ACTH sec retion in the rat. (C) 2000 Elsevier Science B.V. All rights reserved.