Goldbach J M, Roth J, Störr B, Zeisberger E
Physiologisches Institut am Klinikum, Justus-Liebig-Universität, Giessen, Germany.
Eur J Pharmacol. 1997 Jan 29;319(2-3):273-8. doi: 10.1016/s0014-2999(96)00845-x.
In guinea pigs intraperitoneal (i.p.) injections of 50 mg/kg pentoxifylline had no influence on abdominal temperature while higher doses of pentoxifylline caused a hypothermic response lasting for 2-3 h. Administration of 50 mg/kg pentoxifylline 1 h before intramuscular (i.m.) injections of 20 micrograms/kg bacterial lipopolysaccharide reduced the lipopolysaccharide-induced production of endogenous tumor necrosis factor-alpha (TNF-alpha) by 68%. The second phase of lipopolysaccharide-induced fever was significantly attenuated by pretreatment with 50 mg/kg pentoxifylline, a dose which had, per se, no influence on core temperature of guinea pigs. The thermal response of guinea pigs to administration of exogenous TNF-alpha was not modulated by pretreatment with pentoxifylline. Intra-arterial infusions with 5 micrograms/kg TNF-alpha, a dose which yielded the same circulating TNF bioactivity as i.m. injections of 20 micrograms/kg lipopolysaccharide, induced a biphasic febrile response. The magnitude and duration of TNF-induced fever were the same whether guinea pigs were pretreated with pentoxifylline or with 0.9% saline. The results indicate that endogenous formation of TNF-alpha may contribute to the development of fever induced by lipopolysaccharide, but is not its only mediator, since the first phase of lipopolysaccharide-induced fever was not altered by the blockade of TNF production.
在豚鼠中，腹腔注射50毫克/千克己酮可可碱对腹部温度没有影响，而更高剂量的己酮可可碱会引起持续2至3小时的体温过低反应。在肌肉注射20微克/千克细菌脂多糖前1小时给予50毫克/千克己酮可可碱，可使脂多糖诱导的内源性肿瘤坏死因子-α（TNF-α）生成减少68%。用50毫克/千克己酮可可碱预处理可显著减弱脂多糖诱导发热的第二阶段，该剂量本身对豚鼠的核心体温没有影响。己酮可可碱预处理并未调节豚鼠对外源性TNF-α给药的热反应。动脉内输注5微克/千克TNF-α（该剂量产生的循环TNF生物活性与肌肉注射20微克/千克脂多糖相同）可诱导双相发热反应。无论豚鼠是用己酮可可碱还是0.9%生理盐水预处理，TNF诱导发热的幅度和持续时间都相同。结果表明，TNF-α的内源性形成可能有助于脂多糖诱导发热的发展，但不是其唯一介质，因为脂多糖诱导发热的第一阶段并未因TNF生成的阻断而改变。
