MORPHINE STIMULATES PHAGOCYTOSIS OF MYCOBACTERIUM-TUBERCULOSIS BY HUMAN MICROGLIAL CELLS - INVOLVEMENT OF A G-PROTEIN-COUPLED OPIATE RECEPTOR

Opiate-induced immunosuppression has been implicated in the pathogenes is of infections caused by a variety of microorganisms, including huma n immunodeficiency virus (HIV). Although effects of opiates on lymphoc yte function have been studied more extensively, morphine also has bee n shown to inhibit several functional activities of mononuclear phagoc ytes (e.g. chemotaxis, respiratory burst activity and phagocytosis). O piate addiction has been identified as a risk factor for clinical tube rculosis prior to the HIV epidemic, and macrophages are a key cell in the pathogenesis of Mycobacterium tuberculosis. Thus, the hypothesis w as tested in the present study that morphine would suppress phagocytos is of M. tuberculosis by human microglial cells, the resident macropha ges of the brain. Contrary to this hypothesis, treatment of human feta l microglial cell cultures with morphine (10(-8) M) was found to stimu late phagocytosis of nonopsonized M. tuberculosis H37Rv. The stimulato ry effect of morphine was blocked by naloxone and the mu opiate recept or selective antagonist beta-funaltrexamine. Also, morphine-induced in crease in phagocytic activity was markedly inhibited by pertussis toxi n and was unaffected by cholera toxin, suggesting the mechanism of mor phine's stimulatory effect on microglial cell phagocytosis involves a G(i) protein-coupled mu opiate receptor. The results of this in vitro study support the concept that exogenous and endogenous opioids play a n immunomodulatory role within the central nervous system through thei r interaction with G protein-coupled receptors on microglial cells.