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 in the acute phase response. The present study evaluates whether specific opioid receptor subtypes are selectively involved in this immnunomodulatory action. IL-1β was administered either intracerebroventricularly or intraperitoneally at the dose of 400 ng to rats pretreated with the μ-antagonist β- funaltrexamine, the δ-antagonist naltrindole, or the κ-antagonist nor- binaltorphimine, each at the doses of 1, 10, and 100 μg/rat intracerebroventricularly. Serum IL-6 levels were measured 2 h later. The results show that μ-receptor blockade increases, whereas δ-receptor blockade decreases IL-6 induction, suggesting that the fine tuning exerted by opioids on the immune system may be achieved through a balance of opposing effects. Moreover the three antagonists affect IL-6 induction by central and peripheral IL-1β with a similar pattern, indicating that the brain endogenous opioid system plays a general role in the regulation of this cytokine.