PRETREATMENT WITH BETA-FUNALTREXAMINE BLOCKS MORPHINE-MEDIATED SUPPRESSION OF CTL ACTIVITY IN ALLOIMMUNIZED MICE

The effect of prolonged exposure to morphine on cytotoxic T lymphocytes (CTL) and splenic natural killer (NK) activity was investigated. Daily administration of morphine (50.0 mg/kg, s.c.) to alloimmunized mice for 11 days resulted in a significant decrease (25-50%) in peritoneal and splenic CTL activity but not splenic NK activity. To identify the effector cell population mediating cytolysis, cell enrichment studies were carried out. The results of these studies indicated the CTLs are CD8(+) CD4(-). Chronic morphine treatment increased the percentage (25-30%) of CD3(+) CD4(+) and CD8(+) but not Ig(+) cells in the spleen relative to saline-treated controls. Pretreatment of mice with the mu-selective antagonist, beta-funaltrexamine blocked morphine-mediated suppression of splenic and peritoneal CTL activity as well as the increase in CD3(+)CD4(+) and CD8(+) splenic lymphocytes. These results indicate the generation of CTLs in vivo is sensitive to chronic morphine exposure implicating opiates as important co-factors through modulation of cell-mediated immunity.