Chronic morphine administration impairs cell-mediated immune responses in swine

Swine were used as an experimental animal model to evaluate immunomodulating effects of the opiate drug, morphine, on antigen-specific humoral and cell-mediated immune responses. Morphine free base in peanut oil was administered at 4-day intervals for up to 42 days to maintain drug levels at or above 100 ng/ml. The effect of morphine administration on humoral immune responses was evaluated by immunization on day 7 of morphine treatment with a battery of antigens, including swine herpes virus (also known as pseudorabies virus, PRV), Brucella abortus and the Escherichia coli pilus antigens K88, K99, 987P and F41. Fourteen days later, swine were reimmunized with B. abortus and E. coli pilus antigens. Antibody titers to these antigens were evaluated on a weekly basis. Cell-mediated immunity was evaluated by measuring skin immune responses to the antigen 2,4-dintroflurobenozene (DNFB). In one experiment, swine were sensitized with DNFB on day 7 of morphine treatment at the same time as immunization with the other antigens. In a second series of experiments, swine were sensitized either 7 days before or 7 days after initiation of morphine treatment. Pigs were challenged with DNFB administered 27 days after the initiation of morphine treatment and skin responses were evaluated 24 h later. The ability of swine to resist PRV infection was evaluated by exposure to virulent virus on day 28 of morphine treatment. Chronic morphine administration did not impair the induction of the humoral immune responses to bacterial or viral antigens. In addition, morphine treatment did not alter the resistance of immunized swine to PRV infection. In contrast, the cutaneous response to DNFB in morphine-treated swine was markedly suppressed. The suppressed dermal response to DNFB in swine previously sensitized to DNFB either 7 days before or 7 days after morphine treatment. Taken together, these findings indicate that pigs are a suitable animal model to examine the effects of opiate drugs on the immune system and that morphine under a chronic treatment regime suppresses components of cell-mediated, but not humoral immunity.