Previous studies have shown that morphine promotes the replication of human immunodeficiency virus (HIV)-1 in peripheral blood mononuclear cell cocultures. In the present study, we tested the hypothesis that morphine would amplify HIV-1 expression in the chronically infected promonocytic clone U1 when cocultured with lipopolysaccharide-stimulated human fetal brain cells. Marked upregulation of HIV-1 expression was observed in these cocultures (quantified by measurement of HIV-1 p24 antigen levels in supernatants), and treatment of brain cells with morphine resulted in a bell-shaped dose-dependent enhancement of viral expression. The mechanism of morphine's amplifying effect appears to be opioid receptor-mediated and to involve enhanced production of tumor necrosis factor-α by microglial cells.
Bibliographical noteFunding Information:
We thank Dr. StephenC ruikshankfo r his advice, Dr. Monica Tsang for providinga ntibodiest o cytokines,a nd JacquelineO stroumf or help in preparation of the manuscriptT.h is work was supportedin part by United StatesP ublic Health ServicesG rants DA-04381,T 32-DA-07239a, nd AI-27661 and a grant from HennepinF acultyA ssociates.
- Human brain cell culture
- Human immunodeficiency virus-1
- Tumor necrosis- factor-α