MU-opioid receptor-knockout mice: role of mu-opioid receptor in morphine mediated immune functions.

The role of the mu-opioid receptor in immune function was investigated using mu-opioid receptor knockout mice (MOR-KO). Morphine modulation of several immune functions, including macrophage phagocytosis and macrophage secretion of TNF-alpha, was not observed in the MOR-KO animals, suggesting that these functions are mediated by the classical mu-opioid receptor. In contrast, morphine reduction of splenic and thymic cell number and mitogen-induced proliferation were unaffected in MOR-KO mice, as was morphine inhibition of IL-1 and IL-6 secretion by macrophages. These latter results are consistent with morphine action on a naloxone insensitive morphine receptor, a conclusion supported by previous studies characterizing a nonopioid morphine binding site on immune cells. Alternatively, morphine may act either directly or indirectly on these cells, by a mechanism mediated by either delta or kappa opioid receptors.