Site-specific modulation of LPS-induced fever and interleukin-1 expression in rats by interleukin-10

Ledeboer, Annemarie, Rob Binnekade, John J. P. Brevé, John G. J. M. Bol, Fred J. H. Tilders, and AnneMarie Van Dam. Site-specific modulation of LPS-induced fever and interleukin-1 expression in rats by interleukin-10. Am J Physiol Regulatory Integrative Comp Physiol 282: R1762–R1772, 2002. First published February 7, 2002; 10.1152/ajpregu.00766.2001.—Bacterial lipopolysaccharide (LPS) induces fever that is mediated by pyrogenic cytokines such as interleukin (IL)-1 . We hypothesized that the antiinflammatory cytokine IL-10 modulates the febrile response to LPS by suppressing the production of pyrogenic cytokines. In rats, intravenous but not intracerebroventricular infusion of IL-10 was found to attenuate fever induced by peripheral administration of LPS (10 g/kg iv). IL-10 also suppressed LPS-induced IL-1 production in peripheral tissues and in the brain stem. In contrast, central administration of IL-10 attenuated the febrile response to central LPS (60 ng/rat icv) and decreased IL-1 production in the hypothalamus and brain stem but not in peripheral tissues and plasma. Furthermore, intravenous LPS upregulated expression of IL-10 receptor (IL-10R1) mRNA in the liver, whereas intracerebroventricular LPS enhanced IL-10R1 mRNA in the hypothalamus. We conclude that IL-10 modulates the febrile response by acting in the periphery or in the brain dependent on the primary site of inflammation and that its mechanism of action most likely involves inhibition of local IL-1 production.