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 we developed an experimental model where we studied the combined effects of morphine treatment and protein malnutrition. We treated protein-undernourished mice daily for 11 weeks with increasing doses of morphine. Morphine treatment produced a decrease in body weight and spleen cell number. The changes observed were partially independent of the nutritional status of the host. Saline-injected mice showed a decrease in the percentage of Thy 1+ cells in the spleen. Morphine treatment induced a decrease in the total number of cells and therefore in the absolute number of T-(Thy 1, CD4, CD8), B- and Mac 1+ (macrophages) cells in protein-undernourished mice. Saline-injected mice showed a decrease in 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 studied the effects of i.p. administered morphine on expression of thymocyte phenotype in well-nourished and protein-undernourished mice. In well-nourished mice, morphine treatment reduced the number of Thy 1+, CD4+ and CD8+ cells per thymus to 30% of that found in untreated mice and to 40% of the cells in those saline-treated controls. In protein-undernourished mice the absolute number of Thy 1+, CD4+ and CD8+ cells per thymus in morphine-treated mice was reduced to 4% of that in untreated controls, and 8-10% of that in saline-injected mice. The results suggest that morphine has a striking effect on T-cell proliferation that is even more marked when protein-undernutrition is associated.
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