Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression |
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Authors: | Layé S Gheusi G Cremona S Combe C Kelley K Dantzer R Parnet P |
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Institution: | Institut National de la Recherche Agronomique-Institut National de la Santé et de la Recherche Médicale Unité 394, Neurobiologie Intégrative, 33077 Bordeaux, France. s.laye@neurocyto.ubordeaux.fr |
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Abstract: | 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 microgram/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/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, LPS-induced increases in plasma levels of IL-1beta 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. |
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