Töllner B, Roth J, Störr B, Martin D, Voigt K, Zeisberger E
Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Germany.
Pflugers Arch. 2000 Oct;440(6):925-32. doi: 10.1007/s004240000386.
The role of tumor necrosis factor (TNF) in the febrile and metabolic responses of rats to intraperitoneal injection of a high dose of lipopolysaccharide Injection of a high dose of lipopolysaccharide (LPS) induces a septic-shock-like state, which can be accompanied by phases of hypothermia and phases of fever. In the present study we monitored body core temperature and locomotor activity, both by remote radiotelemetry, as well as changes in food intake, body mass and water intake for 3 days after an intraperitoneal (i.p.) injection of a high dose of LPS (5 mg/kg) along with sterile 0.9% saline or a neutralizing form of the soluble tumor necrosis factor (TNF) type 1 receptor (referred to as TNF-binding protein, TNF bp). Intraperitoneal injection of LPS rapidly induced high concentrations of TNF in the plasma and peritoneal lavage fluid. TNF was undetectable in the plasma and peritoneal lavage fluid of animals co-injected with LPS and TNF bp, implying neutralization of peripheral bioactive TNF. Administration of LPS induced hypothermia by about 1.5 degrees C, which lasted for 5 h after injection. During the light-time periods of days 2 and 3 after injection, the rats developed a robust fever. Treatment with TNF bp resulted in a faster recovery from the LPS-induced hypothermia so that the rats developed a pronounced fever on the day of injection. Locomotor activity during night-time periods was suppressed in LPS-treated animals. The LPS-induced depression of night-time activity was not antagonized by co-injection of TNF bp. On day 1 after the injection of LPS, food intake reduced to virtually zero, water intake fell to about 30% of the control value and body mass dropped by 25 g (about 10% of total body mass). With the exception of body mass, these variables recovered slowly during days 2 and 3 after LPS injection, but did not reach the control values. The LPS-induced decreases in food intake, body mass and water intake were significantly attenuated by the treatment with TNF bp. These results confirm that TNF contributes significantly to the rats' responses to intraperitoneal injection of a high dose of LPS. The fact that treatment with TNF bp accelerated and improved the rats' ability to develop a febrile response supports the view that the fever is beneficial, since all other metabolic responses measured in this study were normalized more effectively in those rats that developed a faster and more pronounced increase in body temperature.
肿瘤坏死因子（TNF）在大鼠腹腔注射高剂量脂多糖后的发热和代谢反应中的作用 注射高剂量脂多糖（LPS）可诱导类似败血症休克的状态，可能伴有体温过低期和发热期。在本研究中，我们通过远程无线电遥测监测了大鼠的核心体温和运动活动，以及在腹腔注射高剂量LPS（5 mg/kg）加无菌0.9%生理盐水或可溶性肿瘤坏死因子（TNF）1型受体的中和形式（称为TNF结合蛋白，TNF bp）后3天内的食物摄入量、体重和饮水量变化。腹腔注射LPS迅速诱导血浆和腹腔灌洗液中TNF浓度升高。在同时注射LPS和TNF bp的动物的血浆和腹腔灌洗液中未检测到TNF，这意味着外周生物活性TNF被中和。给予LPS可使体温降低约1.5℃，注射后持续5小时。在注射后第2天和第3天的光照期，大鼠出现强烈发热。用TNF bp治疗可使大鼠从LPS诱导的体温过低中更快恢复，从而在注射当天出现明显发热。LPS处理的动物夜间运动活动受到抑制。同时注射TNF bp并未拮抗LPS诱导的夜间活动抑制。注射LPS后第1天，食物摄入量几乎降至零，饮水量降至对照值的约30%，体重下降25 g（约占总体重的10%）。除体重外，这些变量在LPS注射后第2天和第3天缓慢恢复，但未达到对照值。用TNF bp治疗可显著减轻LPS诱导的食物摄入量、体重和饮水量下降。这些结果证实TNF对大鼠腹腔注射高剂量LPS的反应有显著贡献。用TNF bp治疗加速并改善了大鼠产生发热反应的能力，这一事实支持了发热有益的观点，因为在本研究中测量的所有其他代谢反应在体温升高更快、更明显的大鼠中更有效地恢复正常。
