Zhao Wei, An Huazhang, Zhou Jun, Xu Hongmei, Yu Yizhi, Cao Xuetao
Institute of Immunology and State Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, PR China.
Immunol Lett. 2007 Feb 15;108(2):137-42. doi: 10.1016/j.imlet.2006.11.008. Epub 2006 Dec 19.
Fever influences multiple parameters of the immune response. However, the mechanisms by which fever manipulates immune response remain undefined. Here we present the evidences that fever range hyperthermia differentially regulates immune response to lipopolysaccharide (LPS) and lipoteichoic acids (LTA) through modulating Toll-like receptor (TLR) signaling. Pretreatment with 39.5 degrees C temperature enhanced LPS, but not LTA, induced NF-kappaB activation and TNF-alpha, IL-6 production in human macrophages. Consistently, expression of TLR4, but not TLR2, was up-regulated by 39.5 degrees C treatment. The increase in LPS-induced cytokine production was inhibited by TLR4-blocking antibody, indicating the enhancement of LPS-induced cytokine production by 39.5 degrees C pretreatment was TLR4-dependent. Pretreatment of mice with 39.5 degrees C temperature also enhanced LPS, but not LTA, induced TNF-alpha and IL-6 production in vivo. These results support the concept that fever range hyperthermia might activate innate immune response by promoting TLR4 expression and signaling, providing a possible mechanistic explanation for the function of fever in regulating innate immune responses.
发热会影响免疫反应的多个参数。然而，发热调控免疫反应的机制仍不明确。在此，我们提供证据表明，发热范围的高温通过调节Toll样受体（TLR）信号通路，对脂多糖（LPS）和脂磷壁酸（LTA）的免疫反应进行差异性调节。在39.5摄氏度预处理可增强LPS（而非LTA）诱导的人巨噬细胞中核因子κB（NF-κB）的激活以及肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）的产生。同样，39.5摄氏度处理可上调TLR4（而非TLR2）的表达。TLR4阻断抗体可抑制LPS诱导的细胞因子产生增加，这表明39.5摄氏度预处理增强LPS诱导的细胞因子产生是依赖TLR4的。用39.5摄氏度对小鼠进行预处理也可增强LPS（而非LTA）在体内诱导的TNF-α和IL-6的产生。这些结果支持了这样一个概念，即发热范围的高温可能通过促进TLR4表达和信号传导来激活先天免疫反应，为发热在调节先天免疫反应中的作用提供了一种可能的机制解释。
