Interleukin-1 induces analgesia in mice by a central action

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.