MORPHINE-INDUCED ALTERATIONS IN THYMOCYTE SUBPOPULATIONS OF B6C3F1 MICE

Morphine has been reported to possess immunosuppressive actions in bot h in vitro as well as in vivo assays of immune function. Our work in f emale B6C3F1 mice, surgically implanted with a 75-mg time release morp hine pellet, has confirmed previous reports of a rapid loss in the cel lularity of the spleen and thymus. To evaluate the effect of morphine on the subpopulations of cells in the thymus, two color fluorescence f low cytometry studies were performed. Fluorescently conjugated monoclo nal antibodies specific for the murine cell surface CD4 and CD8 marker s were used to identify the four major subpopulations of thymocytes. T hese studies indicated that morphine pellet-implanted mice suffered a loss in each of the four thymocyte subpopulations in comparison to pla cebo-implanted mice. However, the loss (>90%) in the important CD4+/CD 8+ subpopulation of immature thymocytes greatly exceeded that which wa s observed for any other subpopulation. Kinetic studies of morphine's effect on the thymocyte subpopulations revealed that the maximal deple tion of the CD4+/CD8+ cells occurs approximately 4 days after pellet i mplantation. Thymocyte cell populations recovered by 14 days, with an increase above placebo for the double positive cells. Naltrexone admin istration blocked thymic alterations, suggesting that these immunologi c consequences of morphine may be mediated through an opiate receptor. Measurements in thymocytes from morphine pellet-implanted mice showed an increased level of DNA fragmentation, whereas in vitro exposure to morphine (1-100 muM) produced no such increases. This suggests morphi ne may be working indirectly to induce apoptosis of immature thymocyte s.