Presence of a reduced opioid response in interleukin-6 knock out mice

Cytokines are known to influence neuronal functions. The purpose of this st udy was to investigate the putative role of the cytokine interleukin-6 (IL- 6) in the pathways involved in opioid-mediated responses, by using IL-6-def icient mice. We reported that with a thermal stimulus IL-6-knock-out (IL-6K O) mice presented nociceptive thresholds similar to those measured in their controls. However, they showed a reduced analgesic response both to the re straint stress and to the administration of low doses of morphine. Hypothal amic levels of the opioid peptide beta-endorphin were significantly higher in IL-6KO mice than they were in their controls. The development of toleran ce to the analgesic effect of morphine was more rapid in IL-6-deficient mic e than in wild-type controls. Binding experiments showed that the number of opioid receptors in the midbrain, but not in the hypothalamus, decreased i n IL-6KO mice. Autoradiographic binding analysis revealed that the density of mu receptors diminished while the delta-opioid receptors did not. These results suggest that IL-6 is necessary for a correct development of neurona l mechanisms involved in the response to both endogenous and exogenous opia tes.