Loss of Morphine–induced Suppression of NK Cell activity and T-cell Functions in μ-Opioid Receptor Knockout Mice

In vivo administration of µ-opioid receptor selective agonists to various species is known to suppress lymphocyte, NK cell, and macrophage functions, in addition to mediate pain relief and euphoria. Using a mouse model in which the µ-opioid receptor gene was disrupted by targeted homologous recombination, we explored the involvement of this receptor in natural killer (NK) cell activity and T lymphocyte function. Following peripheral morphine administration, NK cell activity was not affected in homozygous µ-opioid receptor knockout mice, heterozygous animals marginally responded to the immunosuppressive effects of the drug, while wild-type animals were significantly suppressed. In addition, splenic T-cell proliferative responses to concanavalin A, phytohemaglutinin and an antibody to T-cell receptorabαβ (TCR) plus interleukin-2 were not affected by morphine treatment in µ-opioid receptor knockout homozygous and heterozygous mice, whereas morphine significantly suppressed T-cell proliferation in wild-type mice. Taken together, these results suggest a role of the µ-opioid receptor in immunoregulation.