Nakamura H, Nakanishi K, Kita A, Kadokawa T
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Eur J Pharmacol. 1988 Apr 27;149(1-2):49-54. doi: 10.1016/0014-2999(88)90040-4.
The effect of interleukin-1 together with lipopolysaccharide, tumor necrosis factor and interferon on a pain-like response was investigated with the phenylquinone-induced writhing test in mice. Recombinant human interleukin-1 alpha (rHu-IL-1 alpha) inhibited writhing dose relatedly at doses of 0.25-5 micrograms/kg i.v., and its potency was about 1000 times that of morphine on a molar basis. Potent anti-writhing activity was also seen after an i.v. dose of recombinant human tumor necrosis factor (rHu-TNF) and mouse alpha-interferon (mIFN alpha). Lipopolysaccharide, unlike rHu-IL-1 alpha, needed a lag time of about 1 h to develop its anti-writhing action. The relative potency ratios of intracisternal to i.v. and i.p. to i.v. administration of rHu-IL-1 alpha were about 38 and 0.1, respectively. The activity of rHu-IL-1 alpha and rHu-TNF, unlike mIFN alpha, was not naloxone-reversible. rHu-IL-1 alpha did not produce an increase in writhes counts even if injected directly into the peritoneal cavity. These results suggest that rHu-IL-1 alpha, as well as lipopolysaccharide, rHu-TNF and mIFN alpha, had potent anti-writhing activity when given i.v. and its action is due to a central mechanism but is not naloxone-reversible, and that rHu-IL-1 alpha is not algesic under the experimental conditions used.
采用苯醌诱发小鼠扭体试验，研究白细胞介素-1与脂多糖、肿瘤坏死因子及干扰素对疼痛样反应的影响。重组人白细胞介素-1α（rHu-IL-1α）静脉注射剂量为0.25 - 5微克/千克时，剂量依赖性地抑制扭体反应，按摩尔计算其效力约为吗啡的1000倍。静脉注射重组人肿瘤坏死因子（rHu-TNF）和小鼠α干扰素（mIFNα）后也观察到强效的抗扭体活性。与rHu-IL-1α不同，脂多糖产生抗扭体作用需要约1小时的延迟时间。rHu-IL-1α脑池内给药与静脉注射、腹腔注射与静脉注射的相对效价比分别约为38和0.1。与mIFNα不同，rHu-IL-1α和rHu-TNF的活性不能被纳洛酮逆转。即使直接注入腹腔，rHu-IL-1α也不会增加扭体次数。这些结果表明，rHu-IL-1α以及脂多糖、rHu-TNF和mIFNα静脉给药时具有强效抗扭体活性，其作用归因于中枢机制，但不能被纳洛酮逆转，并且在所用实验条件下rHu-IL-1α不具有致痛作用。
