Morphine inhibits CD8+ T cell-mediated, noncytolytic, anti-HIV activity in latently infected immune cells.
Opiates have profound effects on the function of human immune cells and are a possible cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease. We investigated the impact of morphine on CD8+ T cell-mediated, noncytotoxic, anti-HIV activity in latently infected human immune cells. Morphine inhibited the noncytotoxic, anti-HIV activity of CD8+ T cells in HIV latently infected cells (U1 and J1.1). Naltrexone abrogated the morphine-mediated, inhibitory effect on the noncytotoxic, anti-HIV activity of CD8+ T cells. Interferon-gamma (IFN-gamma), a potent antiviral cytokine produced by CD8+ T cells, was partially responsible for CD8+ T cell-mediated, noncytotoxic, anti-HIV activity. The anti-HIV activity of IFN-gamma was also compromised by morphine treatment. Further, morphine attenuated CD8+ T cell-mediated suppression of the HIV long-terminal repeat promoter activation. Morphine also inhibited CD8+ T cell-induced expression of the signal transducer and activator of transcription-1, an important transcriptional factor in the IFN signaling pathway. These data provide additional evidence to support the notion that opioids play a role in impairing the anti-HIV function of the immune system.
The Children's Hospital of Philadelphia, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA.
Xu
X
Wang
Ning
N
Tan
Steven D
SD
Douglas
Ting
T
Zhang
Yan-Jian
YJ
Wang
Wen-Zhe
WZ
Ho
D019380:Anti-HIV Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D019169:Jurkat Cells; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology
D019380:Anti-HIV Agents; D050794:STAT1 Transcription Factor; D009271:Naltrexone; D009020:Morphine; D007371:Interferon-gamma