Effects of in vitro and in vivo opioids on the production of IL-12 and IL-10 by murine macrophages

We evaluated the ability of the specific R opioid receptor agonist DAMGO, the kappa-specific agonist U-50488 in vitro, and exogenous opioid morphine administered in vivo both acutely and chronically to modulate IL-12 and IL-10 production by murine peritoneal macrophages. DAMGO and U-50488 at the concentrations of 10(-6) and 10(-8) M decreased the production of IL-12 without affecting IL-10. One hour after the acute administration of 5, 10, and 20 mg/kg of morphine a dose-related decrease of both IL-10 and IL-12 levels was present. The pretreatment with naltrexone at doses up to 20 mg/kg did not prevent the decrease of IL-10 and IL-12 induced by morphine. When the drug was administered chronically, a differential development of tolerance to the immune effects was observed. After 3 days of treatment the effect of the acute challenge with 20 mg/kg of morphine on IL-12 was lost. In contrast, morphine-induced inhibition of IL-10 disappeared between 10 and 12 days of treatment, in parallel with tolerance to the antinociceptive effect. These results suggest that opioids modulate macrophage cytokine production. However, the effects exerted by the in vivo administration of morphine are not superimposable onto those induced by the in vitro administration of specific opioid agonists.