AREGU July 48/1

Layé, Sophie, Gilles Gheusi, Sandrine Cremona, Chantal Combe, Keith Kelley, Robert Dantzer, and Patricia Parnet. Endogenous brain IL-1 mediates LPSinduced anorexia and hypothalamic cytokine expression. Am J Physiol Regulatory Integrative Comp Physiol 279: R93– R98, 2000.—The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5–10 μg/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1b, IL-6, and tumor necrosis factor-a) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1b. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 μg/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPSinduced increases in plasma levels of IL-1b were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.