Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats.

We assessed the effect of interleukin-6 (IL-6) in the brain on nociception by using the hot-plate test in rats. Recombinant human IL-6 (rhIL-6, 30 pg-300 ng) was microinjected into the lateral cerebroventricle (LCV) and the paw-withdrawal latency was then measured for 60 min after injection. RhIL-6 at 300 pg reduced the paw-withdrawal latency at 15 min after injection. Further increase of rhIL-6 doses to 3, 30 and 300 ng resulted in the decreased paw-withdrawal latency at 15 and 30 min. Although the peak responses observed at 3-300 ng did not differ significantly, the time taken for recovery tended to be longer with increasing doses. The rhIL-6 (30 ng)-induced reduction of the paw-withdrawal latency was completely blocked by the co-injection of either Na salicylate (30 ng, LCV) or alpha-melanocyte stimulating hormone (30 ng, LCV), an anti-cytokine substance. However, it was not affected by the co-injection of IL-1 receptor antagonist (30 ng, LCV) which had been previously shown to be able to block IL-1 beta-induced hyperalgesia. These findings indicate that IL-6 in the brain induces hyperalgesia by its prostanoids-dependent action in rats. The hyperalgesic action of central IL-6 thus does not appear to depend on the action of IL-1.