Klir J J, McClellan J L, Kozak W, Szelényi Z, Wong G H, Kluger M J
Institute for Basic and Applied Medical Research, Lovelace Institutes, Albuquerque, New Mexico 87108.
Am J Physiol. 1995 Feb;268(2 Pt 2):R480-6. doi: 10.1152/ajpregu.1995.268.2.R480.
The purpose of this study was to test the hypothesis that tumor necrosis factor-alpha (TNF) limits fever induced by lipopolysaccharide (LPS) in rats and to determine whether such antipyretic action of this cytokine is outside or inside the central nervous system (CNS). The CNS effects on LPS-induced fever were tested by injecting a subpyrogenic amount (0.20 microgram) of human recombinant TNF (hrTNF) intracerebroventricularly or by slowly infusing into the anterior hypothalamus an amount previously measured in this brain region during LPS fever (0.24 U in 0.13 microliter of artificial cerebrospinal fluid/min). The peripheral effects of this cytokine on LPS fever were tested by injecting 1 micrograms/kg of hrTNF intraperitoneally or by intraperitoneal administration of 300 micrograms/kg of the hrTNF soluble receptor p80 (hrTNFsr). The core temperature (measured by biotelemetry) during LPS fever was not significantly affected by administration of hrTNF intracerebroventricularly or intrahypothalamically. An intraperitoneal injection of hrTNF (1 microgram/kg) had a significant antipyretic effect on febrile response to LPS (mean temperature 2-8 h after injections was 37.28 +/- 0.12 degrees C in rats injected with hrTNF and LPS vs. 38.73 +/- 0.04 degrees C in rats injected with saline and LPS; analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). When rats were injected intraperitoneally with hrTNFsr, the febrile response to LPS was enhanced (analysis of variance among groups, P = 0.0001; Fisher's protected least significant difference, P < 0.05). These results support the hypothesis that TNF acts to limit the magnitude of LPS-induced fever and that this action occurs outside the CNS.
本研究的目的是检验肿瘤坏死因子-α（TNF）限制大鼠体内脂多糖（LPS）诱导发热的假说，并确定这种细胞因子的解热作用是在中枢神经系统（CNS）之外还是之内。通过脑室内注射亚致热剂量（0.20微克）的人重组TNF（hrTNF），或通过将先前在LPS发热期间在该脑区测得的量（0.24单位，以0.13微升人工脑脊液/分钟的速度缓慢注入下丘脑前部）来测试CNS对LPS诱导发热的影响。通过腹腔注射1微克/千克的hrTNF或腹腔注射300微克/千克的hrTNF可溶性受体p80（hrTNFsr）来测试这种细胞因子对LPS发热的外周影响。LPS发热期间的核心温度（通过生物遥测测量）不受脑室内或下丘脑内注射hrTNF的显著影响。腹腔注射hrTNF（1微克/千克）对LPS引起的发热反应有显著的解热作用（注射hrTNF和LPS的大鼠在注射后2 - 8小时的平均体温为37.28±0.12℃，而注射生理盐水和LPS的大鼠为38.73±0.04℃；组间方差分析，P = 0.0001；Fisher保护最小显著差异，P < 0.05）。当给大鼠腹腔注射hrTNFsr时，对LPS的发热反应增强（组间方差分析，P = 0.0001；Fisher保护最小显著差异，P < 0.05）。这些结果支持了TNF限制LPS诱导发热幅度且这种作用发生在CNS之外的假说。
