Immunosuppressive effects of dihydroetorphine, a potent narcotic analgesic, in dihydroetorphine-dependent mice

The immunomodulatory effects of dihydroetorphine were systematically invest igated in subchronically treated mice. In a dose-dependent fashion, dihydro etorphine (total doses at 444.5, 889 and 1778 mu g/kg) lowered the increase of body weight, decreased the weight of the spleen and thymus, weakened th e delayed-type hypersensitivity, reduced the generation of antibody-forming cells, inhibited splenic lymphocyte proliferation induced by concanavalin A and lipopolysaccharide, suppressed the production of interleukin-2 in the supernatant of splenocytes induced by concanavalin A, and depleted the rat io of CD4(+) and CD8(+) subpopulations. Moreover, the physical dependence o n dihydroetorphine was also evaluated to confirm that the immunosuppression was concomitant with the addiction to thr drug. These results demonstrate that subchronic treatment with dihydroetorphine dose dependently suppresses both humoral and cell-mediated immune function, and that the immunosuppres sive effects of dihydroetorphine are much more potent than those of morphin e. (C) 1999 Elsevier Science B.V. All rights reserved.