Ledeboer Annemarie, Binnekade Rob, Brevé John J P, Bol John G J M, Tilders Fred J H, Van Dam Anne-Marie
Research Institute Neurosciences Free University, Department of Medical Pharmacology, VU University Medical Center, 1081 BT Amsterdam, The Netherlands.
Am J Physiol Regul Integr Comp Physiol. 2002 Jun;282(6):R1762-72. doi: 10.1152/ajpregu.00766.2001.
Bacterial lipopolysaccharide (LPS) induces fever that is mediated by pyrogenic cytokines such as interleukin (IL)-1 beta. We hypothesized that the anti-inflammatory 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 microg/kg iv). IL-10 also suppressed LPS-induced IL-1 beta 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 beta 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 beta production.
细菌脂多糖（LPS）可诱导发热，该过程由白细胞介素（IL）-1β等致热细胞因子介导。我们推测抗炎细胞因子IL-10通过抑制致热细胞因子的产生来调节对LPS的发热反应。在大鼠中，发现静脉注射而非脑室内注射IL-10可减轻外周给予LPS（10微克/千克静脉注射）所诱导的发热。IL-10还可抑制外周组织和脑干中LPS诱导的IL-1β产生。相反，脑室内给予IL-10可减轻对脑室内LPS（60纳克/大鼠脑室内注射）的发热反应，并降低下丘脑和脑干中IL-1β的产生，但对外周组织和血浆中的IL-1β产生无影响。此外，静脉注射LPS可上调肝脏中IL-10受体（IL-10R1）mRNA的表达，而脑室内注射LPS可增强下丘脑中IL-10R1 mRNA的表达。我们得出结论，IL-10通过根据炎症的主要部位在外周或脑内发挥作用来调节发热反应，其作用机制很可能涉及抑制局部IL-1β的产生。
