Morphine suppresses primary humoral immune responses by a predominantly indirect mechanism

Morphine suppresses humoral immune responses, causes thymic hypoplasia and suppresses NK (natural killer) activity in animal models. There is evidence that thymic hypoplasia and NK suppression are predominantly mediated by indirect mechanisms. The mechanism of morphine-induced humoral immunosuppression is less certain. Recent reports suggest that morphine and other opioids can directly act on cells of the immune system to suppress the generation of antibody-forming cells (AFC) in Mishell-Dutton cultures. The present study was designed to assess the roles of direct and indirect mechanisms in morphine-induced suppression of humoral immunity. Splenocytes from mice treated with morphine by s.c. implantation of a slow-release 75 mg pellet were dysfunctional in Mishell-Dutton cultures. Exposure to morphine in vivo for 12 or 24 hr caused significant suppression of the AFC production stimulated by sheep erythrocytes in Mishell-Dutton cultures. In contrast, direct addition of morphine or the kappa selective opioid agonist U50,488H to Mishell-Dutton cultures under a variety of conditions had little or no effect on AFC generation. These results indicate that suppression of humoral responses by morphine is not primarily mediated by direct action of morphine on the immune system. Suppression of AFC responses by administration of morphine in vivo was substantially blocked by treating mice with the glucocorticoid antagonist RU 38486, suggesting that glucocorticoids may be involved in the indirect mechanism by which morphine causes splenocyte dysfunction.