INTERLEUKIN-6 IS DIFFERENTLY MODULATED BY CENTRAL OPIOID RECEPTOR SUBTYPES

The central endogenous opioid system is involved in the modulation of interleukin (IL)-6, an inflammatory cytokine that plays a major role i n the acute phase response. The present study evaluates whether specif ic opioid receptor subtypes are selectively involved in this immunomod ulatory action. IL-1 beta was administered either intracerebroventricu larly or intraperitoneally at the dose of 400 ng. to rats pretreated w ith the mu-antagonist beta-funaltrexamine, the delta-antagonist naltri ndole, or the kappa-antagonist nor-binaltorphimine, each at the doses of 1, 10, and 100 mu g/rat intracerebroventricularly. Serum IL-6 level s were measured 2 h later. The results show that mu-receptor blockade increases, whereas delta-receptor blockade decreases IL-6 induction, s uggesting that the fine tuning exerted by opioids on the immune system may be achieved through a balance of opposing effects. Moreover the t hree antagonists affect IL-6 induction by central and peripheral IL-1 beta with a similar pattern, indicating that the brain endogenous opio id system plays a general role in the regulation of this cytokine.