Morphine-induced immunosuppression: Effects of protein kinase C activation in lymphocytes

The present investigation describes effects of morphine on lymphocyte activation. It is reported here that bypassing the early events of signal transduction by direct protein kinase C (PKC) stimulation with phorbol myristate acetate (PMA), the initial increase in interleukin-2 Receptor (IL-2R) expression is decreased in both CD4+ and CD8+ T cells after 48 hours following morphine implantation, and returns to control levels at 72 and 96 hours. Simultaneous administration of the opiate antagonist naltrexone blocked the effect in CD4+ T cells. However, this effect was not reproduced by PMA stimulated splenocytes incubated with morphine (10$\sp{-8}$-10$\sp{-5}$M), suggesting that the effect is mediated through opiate-receptors, but not directly through opiate receptors on T cells. Additionally, adrenalectomy blocked the effect in both CD4+ and CD8+ T cells suggesting that the effects of morphine on PMA stimulated increase in IL-2R expression may be mediated through a glucocorticoid-dependent mechanism in both these T cell subsets. Decreased IL-2R expression, may play a role in opiate-induced immunosuppression.