Immunologic characterization of TAT 72-transgenic mice: Effects of morphine on cell-mediated immunity

Abstract

The immunosuppressive effect of morphine in an HIV-1 transactivator of transcription (TAT)-transgenic mouse model was investigated in order to elucidate possible mechanisms of human immunodeficiency virus (HIV)-1 disease progression. The TAT 72 transgene (1–72 amino acids) was placed under the control of SV40 viral promoter to provide systemic expression. Mice were treated daily for 5 days with morphine (50.0 mg/kg) or vehicle following alloantigen immunization. In TAT-transgenic mice, morphine modestly reduced mitogen-induced IL-2 production, which correlated with reduced percentages of CD4 + and CD8 + splenic lymphocytes. TAT-transgenic animals displayed reduced splenic natural killer (NK) and peritoneal cytotoxic T-lymphocyte (CTL) activities irrespective of morphine treatment. In addition, the effect of morphine on splenic NK and CTL activity was shown to be stereospecific as defined using (+)-morphine (50 mg/kg). Pretreatment of mice with the μ-selective opioid receptor antagonist β-funaltrexamine (40.0 mg/kg) blocked morphine-induced modulation of splenic CTL activity. Since elevated corticosterone levels have previously been associated with immunosuppression following prolonged morphine exposure, serum corticosterone levels were assessed. Reduced serum corticosterone levels were found to be associated with morphine treatment in non-transgenic mice as well as vehicle- or morphine-treated mice. Collectively, the data suggest that the presence of TAT 72 compromises splenic NK activity as well as peritoneal CTL activity and leads to a reduction in serum corticosterone levels. Also, morphine-mediated modulation of the immune system in non-transgenic mice is stereoselective and due in part to μ-opioid receptors.