Leon L R, Kozak W, Peschon J, Kluger M J
Institute for Basic and Applied Medical Research, The Lovelace Institutes, Albuquerque, New Mexico 87108, USA.
Am J Physiol. 1997 Feb;272(2 Pt 2):R563-9. doi: 10.1152/ajpregu.1997.272.2.R563.
We examined the effects of injections of systemic [lipopolysaccharide (LPS), 2.5 mg/kg or 50 pg/kg ip] or local (turpentine, 100 microl sc) inflammatory stimuli on fever, motor activity, body weight, and food intake in tumor necrosis factor (TNF) double receptor (TNFR)-knockout mice. A high dose of LPS resulted in exacerbated fevers in TNFR-knockout mice compared with wild-type mice for the early phase of fever (3-15 h); the late phase of fever (16-24 h) and fevers to a low dose of LPS were similar in both groups. Motor activity, body weight, and food intake were similarly reduced in both groups of mice after LPS administration. In response to turpentine, TNFR-knockout and wild-type mice developed virtually identical responses to all variables monitored. These results suggest that 1) TNF modulates fevers to LPS dose dependently, 2) TNF does not modulate fevers to a subcutaneous injection of turpentine, and 3) knockout mice may develop cytokine redundancy in the regulation of the acute phase response to intraperitoneally injected LPS or subcutaneously injected turpentine.
我们研究了全身性注射[脂多糖（LPS），2.5毫克/千克或50皮克/千克腹腔注射]或局部注射（松节油，100微升皮下注射）炎性刺激对肿瘤坏死因子（TNF）双受体（TNFR）基因敲除小鼠发热、运动活性、体重和食物摄入量的影响。在发热早期（3 - 15小时），与野生型小鼠相比，高剂量LPS导致TNFR基因敲除小鼠发热加剧；两组在发热后期（16 - 24小时）以及对低剂量LPS的发热反应相似。给予LPS后，两组小鼠的运动活性、体重和食物摄入量均有类似程度的降低。对松节油的反应，TNFR基因敲除小鼠和野生型小鼠对所有监测变量产生几乎相同的反应。这些结果表明：1）TNF对LPS引起的发热具有剂量依赖性调节作用；2）TNF对皮下注射松节油引起的发热无调节作用；3）基因敲除小鼠在对腹腔注射LPS或皮下注射松节油的急性期反应调节中可能出现细胞因子冗余现象。
