Morphine-Induced Suppression of Thymocyte Proliferation is Mediated by Inhibition of IL-2 Synthesis

Abstract

A correlation between chronic morphine use and immunosuppression has been well established in the recent past. The mechanisms responsible for these morphine induced changes in the immune system are unknown. There is evidence to show that this immunosuppression may be mediated either (1) directly through opiate receptors present on lymphocytes (Sibinga and Goldstein, 1988; Carr et al., 1988), (2) indirectly through opiate receptors in the central nervous system, or (3) by activation of the hypothalamic-pituitaryadrenal axis (George and Way, 1955) to release immunosuppressive glucocorticoid (Byat etal., 1991). Normal thymocytes and resting T-lymphocytes express low-affinity morphine receptors (Kd ~100 nM) (Madden et al., 1990; Roy et al., 1991). In addition, we have demonstrated that interleukin-1 (IL-1) activation of thymocytes results in a dramatic increase in specific binding of ³H-morphine on activated T-cells (Roy et al., 1991) This increase in binding results from both an increase in affinity (Kd 30 NM) as well as an increase in the number of receptors (Bmax). The physiological role of these binding sites is unknown. We hypothesize that induction of high affinity binding sites may directly mediate the effects of morphine on activated thymocytes and T-lymphocytes.