Immunologic effects of morphine administration in rabbits.

Long-term effects of morphine administration or immunologic test responses were studied in female rabbits. Implantation of morphine-containing pellets was found to be more effective than injection of morphine sulfate solutions in promoting increased serum binding of 140-morphine. A large part of the increased morphine binding by sera associated with administration of morphine was found in serum fractions containing gamma-globulin and was absent in gamma-globulin-free fractions. These sera showed some degree of specificity for the morphine configuration in tests with other narcotics. They also gave positive immunologic test reactions in passive hemagglutination and radial immunodiffusion tests involving serum albumins conjugated with morphine derivatives. Other evidence for immunologic responsiveness against morphine by morphine-pretreated rabbits was shown by cutaneous hypersensitivity reactions against morphine-carrier conjugates and by a diminution of the serum morphine-binding response in rabbits given an immunosuppressive dose of cyclophosphamide. Failure of naloxone, a morphine antagonist, to alter the serum morphine-binding response suggested that serum levels of the morphine-binding globulin studied here were not direclty related to morphine withdrawal.

Immunologic effects of morphine in rodents, rabbits, monkeys, and cats.

The effects of prolonged morphine administration on immunologic reactivity against morphine was studied in a number of animal species: rabbit, monkey, guinea pig, rat, and cat. Some evidence for increased serum binding of 14C-labeled morphine was noted after morphine treatment in all test species, with the rabbit the best responder and the cat showing little or no response. In addition to measurements on serum binding of 14C-labeled morphine, other methods (measurement of serum binding of 14C-labeled codeine and methadone, competitive inhibition tests, radial immunodiffusion, and passive hemagglutination) were used for one or more of the species. Overall, results with these test methods have shown that prolonged morphine administration can result in immunologic responsiveness to morphine in animals.

Effect of antilymphocyte serum (ALS) on shock in rats.

Effects of treatment with rabbit antirat anti-lymphocyte serum and globulin (ALS and ALG) on shock survival were studied in Sprague-Dawley derived male rats. Because of their known cytotoxic capability, it was postulated that lymphocytes might play a role in the pathogenesis of shock and that suppression of lymphocyte function by ALS/ALG treatment should then protect against shock. Shock models used were tourniquet, endotoxin, and hemorrhagic shock. Protection against tourniquet shock was found for ALS made against thymocytes but not for ALS against spleen cells or lymph node cells. The shock-protective factor was found in the ALG-containing serum fraction but not in the primarily albumin fraction. No significant protection was found for ALS treatment against either endotoxin or hemorrhagic shock. ALS effects on blood cell counts, reticulo endothelial system clearance, and inflammation were studied to help identify effects of ALS on shock survival. It was concluded from these studies that thymic or thymus-processed lymphocytes could play a role in the pathogenesis of shock but that multiple effects of ALS/ALG treatment necessitate further studies to elucidate any role for lymphocytes in shock.