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Morphine inhibits CD8+ T cell-mediated, noncytolytic, anti-HIV activity in latently infected immune cells

The Children's Hospital of Philadelphia, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA.
Journal of Leukocyte Biology (Impact Factor: 4.3). 10/2005; 78(3):772-6. DOI: 10.1189/jlb.0305167
Source: PubMed

ABSTRACT 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.

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    • "Morphine suppressed the production of interferon–alpha (IFN-α (Peterson et al. 1989; Wang et al. 2002a), a cytokine that modulates all phases of immune processes and has a central role in host innate immunity against viral infections. We recently showed that morphine, through the suppression of interferon-gamma (IFN-γ), compromised CD8 + T cellmediated anti-HIV activity in both acute and latently infected cells (Wang et al. 2005). Opioids modulates immune functions via pharmacological activation of endogenous opioid receptors in the immune cells (Bayer et al. 1990; Fecho et al. 1996; Hernandez et al. 1993). "
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    • "Wang and colleagues investigated the effect of morphine on CD8 + T cell–mediated, noncytotoxic, anti-HIV activity in latently infected human immune cells and found that these activities were inhibited by morphine. This effect could be abrogated by treatment with naltrexone, providing additional evidence to support the notion that opioids play a role in impairing the anti-HIV function of the immune system (Wang et al, 2005; Friedman et al, 2006). Singhal et al evaluated the molecular mechanism of opiate-induced T-cell apoptosis. "
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    • "The effects of opioids on immune function have been well studied and reviewed (Brinkman, Hall, Suo & Weber, 1998; Donahoe & Vlahov, 1998; Peterson, Molitor & Chao, 1998; Vallejo, Leon-Casasola & Benyamin, 2004). Opioids have been associated with reduced effectiveness of immune cells against HIV (Quand-Cantagrel, Wallace, Ashar & Mathews, 2001; Wang, et al., 2005) and enhanced viral replication (Li, et al., 2002; Peterson et al., 1999; Schweitzer et al., 1991). However, the role of opioids on immune functions is complex, as they may also exert neuroprotective effects (Nath et al., 2002; Stefano, 1999). "
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