Abstract

These studies investigated the potential mechanisms by which acute morphine administration inhibits peripheral blood lymphocyte activity in the rat. As reported previously, blood lymphocyte proliferative responses to concanavalin A were found to be suppressed by 70% 2 hr after administration of morphine (10 mg/kg). In the present study, a more selective mu receptor agonist, fentanyl (0.05 mg/kg), was found to similarly inhibit blood lymphocyte proliferation. Pretreatment with the opioid receptor antagonist naltrexone (5 mg/kg) completely blocked the inhibitory actions of morphine (7 mg/kg). Several different approaches were undertaken to determine whether the depressed blood lymphocyte proliferative response after opioid receptor stimulation was due to an effect on circulating lymphocyte number. First, it was found that morphine administration was accompanied by a 30% decrease in the absolute number of circulating lymphocytes. Fluorescence-activated cell sorter analysis revealed that the decrease was not selective for any specific subpopulation of T lymphocyte. Furthermore, the relative distribution of circulating monocytes, neutrophils or eosinophils was not altered by morphine treatment. The morphine-induced lymphopenia was abolished in adrenalectomized rats, suggesting that this redistribution effect was mediated by the release of adrenal hormones. However, on correcting for the decrease in lymphocyte number by using Ficoll-separated lymphocyte cultures, the proliferative responses of blood lymphocytes remained significantly depressed compared with control values. Collectively, these data suggest that both an adrenal-dependent lymphopenia and an opioid-induced decrease in responsiveness to mitogenic stimulation contribute to the overall antiproliferative effect of morphine on blood lymphocytes.