SPLEEN AND THYMUS-CELL SUBSETS MODIFIED BY LONG-TERM MORPHINE ADMINISTRATION IN PROTEIN-UNDERNOURISHED MICE .1.

Severe infections in intravenous drug abusers could be the consequence of morphine-induced damage on the immune system. To evaluate the long -term effect of in vivo morphine administration on the immune system w e developed an experimental model where we studied the combined effect s of morphine treatment and protein malnutrition. We treated protein-u ndernourished mice daily for 11 weeks with increasing doses of morphin e. Morphine treatment produced a decrease in body weight and spleen ce ll number. The changes observed were partially independent of the nutr itional status of the host. Saline-injected mice showed a decrease in the percentage of Thy 1+ cells in the spleen. Morphine treatment induc ed a decrease in the total number of cells and therefore in the absolu te number of T-(Thy 1, CD4, CD8), B- and Mac 1+ (macrophages) cells in protein-undernourished mice. Saline-injected mice showed a decrease i n the percentage of Thy 1+ cells and an increase in the percentage of B- and Ia+-cells in the spleen. We conclude that morphine altered the immune system by down-regulating splenocyte proliferation. We also stu died the effects of i.p. administered morphine on expression of thymoc yte phenotype in well-nourished and protein-undernourished mice. In we ll-nourished mice, morphine treatment reduced she number of Thy 1+, CD 4+ and CD8+ cells per thymus to 30% of that found in untreated mice an d to 40% of the cells in those saline-treated controls. In protein-und ernourished mice the absolute number of Thy 1+, CD4+ and CD8+ cells pe r thymus in morphine-treated mice was reduced to 4% of that in untreat ed controls, and 8 - 10% of that in saline-injected mice. The results suggest that morphine has a striking effect on T-cell proliferation th at is even more marked when protein-undernutrition is associated.