Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression

The present study was designed to determine the role of endogenous brain in terleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intr aperitoneal administration of LPS (5-10 mu g/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1 beta, IL-6, and tumor necrosis fact or-alpha) in the hypothalamus. This dose of LPS also increased plasma level s of IL-1 beta. Intracerebroventricular pretreatment with IL-1 receptor ant agonist (4 mu g/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cyt okine mRNA measured in the hypothalamus 1 h after treatment. In contrast, L PS-induced increases in plasma levels of IL-1 beta were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the de velopment of the hypothalamic cytokine response to a systemic inflammatory stimulus.