Endogenous opioids modulate allograft rejection time in mice: possible relation with Th1/Th2 cytokines

The continuous infusion of the opioid peptide β‐endorphin prolongs skin allograft survival in mice, while the opiate receptor antagonist naloxone, administered together with the opioid at the time of transplantation, abolishes the effect of the opioid. Consistently, naloxone, when given alone at the time of transplantation, but not later, accelerates graft rejection and increases splenocyte IL‐2 and interferon‐gamma (IFN‐γ) production. Splenocyte β‐endorphin concentrations are lower in transplanted animals. The effects of exogenous β‐endorphin and naloxone suggest that the endogenous opioid peptide β‐endorphin exerts a tonic inhibitory effect over early events of T cell‐mediated immune responses in vivo. The effects of β‐endorphin and naloxone are consistent with the previously shown role of the opioid system in the modulation of the Th1/Th2 cytokine pattern.