The effect of central injection of angiotensin-converting enzyme inhibitor and the angiotensin type 1 receptor antagonist on the induction by lipopolysaccharide of fever and brain interleukin-1beta response in rats.

We recently reported an involvement of peripheral angiotensin II (ANG II) in the development of both the fever and the peripheral interleukin (IL)-1beta production induced in rats by a systemic injection of lipopolysaccharide (LPS). The present study was performed to investigate whether brain ANG II contributes to the fever and IL-1beta production in the rat brain induced by i.c.v. injection of LPS. LPS (0.2 and 2 microg i.c.v.) induced dose-related fevers and increases in the brain (hypothalamus, hippocampus, and cerebellum) concentrations of IL-1beta. These effects were significantly inhibited by i.c.v. administration of either an angiotensin-converting-enzyme (ACE) inhibitor or an angiotensin type 1 (AT(1)) receptor antagonist. By contrast, the ACE inhibitor had no effect on the IL-1beta (i.c.v.)-induced fever, whereas the AT(1) receptor antagonist enhanced (rather than reduced) it. The AT(1) receptor antagonist had no effect on the brain levels of prostaglandin E(2) in rats given an i.c.v. injection of IL-1beta. These results suggest that in rats, brain ANG II and AT(1) receptors are involved in the LPS-induced production of brain IL-1beta, thus contributing to the fever induced by the presence of LPS within the brain.