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INFLAMMATION AND IMMUNOPHARMACOLOGY

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-1 Response in Rats

Division of Integrative Physiology, Department of Functional, Morphological and Regulatory Science, Tottori University Faculty of Medicine, Tottori, Japan

We recently reported an involvement of peripheral angiotensin II (ANG II) in the development of both the fever and the peripheral interleukin (IL)-1 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-1 production in the rat brain induced by i.c.v. injection of LPS. LPS (0.2 and 2 µg i.c.v.) induced dose-related fevers and increases in the brain (hypothalamus, hippocampus, and cerebellum) concentrations of IL-1. These effects were significantly inhibited by i.c.v. administration of either an angiotensin-converting-enzyme (ACE) inhibitor or an angiotensin type 1 (AT₁) receptor antagonist. By contrast, the ACE inhibitor had no effect on the IL-1 (i.c.v.)-induced fever, whereas the AT₁ receptor antagonist enhanced (rather than reduced) it. The AT₁ receptor antagonist had no effect on the brain levels of prostaglandin E₂ in rats given an i.c.v. injection of IL-1. These results suggest that in rats, brain ANG II and AT₁ receptors are involved in the LPS-induced production of brain IL-1, thus contributing to the fever induced by the presence of LPS within the brain.

Address correspondence to: Dr. Tatsuo Watanabe, Division of Integrative Physiology, Department of Functional, Morphological, and Regulatory Science, Tottori University Faculty of Medicine, Yonago, Tottori 683, Japan. E-mail: watanabe{at}grape.med.tottori-u.ac.jp

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