The effect of opiates on the intestinal immune response to cholera toxin in mice

We studied the effect of opiates on the intestinal immunoglobulin A response in mice. C57BL mice were orally immunized by two doses of 10 micrograms of cholera toxin, 2 weeks apart. Experimental groups received subcutaneous injections of morphine, either 10 or 20 mg/kg/day, in two divided doses. Morphine was given for 4 days, starting 1 day prior to each cholera toxin dose. Intestinal secretions were collected by lavage 1 week after the last cholera toxin dose, and assayed for specific anticholera toxin antibody and total immunoglobulin A. Results were expressed as units of anticholera toxin per nanogram immunoglobulin A. It was found that morphine, 20 mg/kg/day, reduced the response from 30.9 +/- 3.11 to 9.78 +2- 1.42 units/ng (M +/- SEM; p less than 0.0001). 10 mg/kg/day of morphine slightly reduced the immune response to 21.38 +/- 3.51 units/ng (M +/- SEM), but failed to achieve statistical significance. Naloxone administration prior to morphine injections abolished the inhibitory effects of morphine. Morphine administration had no effect on the response to a booster dose of cholera toxin 3 months after the initial cholera toxin immunization and morphine administration. It is concluded that morphine has a significant inhibitory effect on the intestinal immune response, but does not effect long-term mucosal immunological memory. The effect is probably mediated by a specific opiate receptor, as it is blocked by naloxone. This effect may have clinical implications.