Hypothalamic neuronal responses to interleukin-6 in tissue slices: effects of indomethacin and naloxone.

We recently reported that human recombinant interleukin-6 (hrIL-6) microinjected into the preoptic area (POA) of guinea pigs induced fever at high doses, suggesting that IL-6 may be another endogenous pyrogen. This study was undertaken to determine whether hrIL-6 affects the single-unit activity of thermosensitive and thermally insensitive neurons in hypothalamic tissue slices and whether indomethacin (Indo) or naloxone (Nal), a cyclooxygenase inhibitor and a mu-opioid receptor antagonist, respectively, influences the effects of hrIL-6 on those neurons. hrIL-6 (2 x 10(3)-8 x 10(3) U/ml) depressed the activity in 50 (83%) of 60 warm-sensitive (W) neurons and excited all 4 cold-sensitive (C) neurons found. It had no effect, however, on 14 (48%) of 29 thermally insensitive (I) neurons, albeit 7 and 8 I neurons decreased and increased their firing rates, respectively. Indo (0.05-1 mg/ml) blocked the effect of hrIL-6 on 22 of 24 W neurons and 2 C neurons tested. Nal(0.1-1 mg/ml) blocked or reduced the effect of hrIL-6 on 21 of 25 W neurons and 1 C neuron recorded. These drugs induced no neuronal response per se. Nal at 2-5 mg/ml, which increased the activity of four W neurons by itself, reversed their depressed response to hrIL-6. These results support the possibility that IL-6-induced fevers may be mediated through an effect on thermosensitive neurons in the POA and that opioids and prostaglandin E may both be involved in this process.