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: 4.29). 10/2005; 78(3):772-6. DOI: 10.1189/jlb.0305167
Source: PubMed


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.

Download full-text


Available from: Wenzhe Ho, Aug 18, 2014
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Human immunodeficiency virus (HIV) infection and progression of acquired immunodeficiency syndrome (AIDS) can be modulated by a number of cofactors, including drugs of abuse. Opioids, cocaine, cannabinoids, methamphetamine (METH), alcohol, and other substances of abuse have been implicated as risk factors for HIV infection, as they all have the potential to compromise host immunity and facilitate viral replication. Although epidemiologic evidence regarding the impact of drugs of abuse on HIV disease progression is mixed, in vitro studies as well as studies using in vivo animal models have indicated that drugs of abuse have the ability to enhance HIV infection/replication. Drugs of abuse may also be a risk factor for perinatal transmission of HIV. Because high levels of viral load in maternal blood are associated with increased risk of HIV vertical transmission, it is likely that drugs of abuse play an important role in promoting mother-fetus transmission. Furthermore, because the neonatal immune system differs qualitatively from the adult system, it is possible that maternal exposure to drugs of abuse would exacerbate neonatal immunity defects, facilitating HIV infection of neonate immune cells and promoting HIV vertical transmission. The availability and use of antiretroviral therapy for women infected with HIV increase, there is an increasing interest in determining the impact of drug abuse on efficacy of AIDS Clinical Trials Group (ACTG)-standardized treatment regimens for woman infected with HIV in the context of HIV vertical transmission.
    Full-text · Article · Nov 2010 · Life sciences
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Both human immunodeficiency virus (HIV) and illicit drug addiction remain major health problems not only in the United States but all over globe. The effect of drug addiction on HIV/AIDS (acquired immunodeficiency syndrome) has been somewhat underexplored. However, in United States more than one fourth of HIV-positive individuals are injection drug users. Opiates are known to negatively affect the immune system, and therefore may have deleterious effects on progression of disease among HIV-infected individuals. This review discusses the effects of opiates on immune system as well as its effect on HIV replication and AIDS progression. In addition, the effects of opiates on disease progression in non-human primate model of AIDS is presented with at least one possible reason for rapid disease progression in multi-virus the challenge model.
    Full-text · Article · Sep 2008 · Journal of NeuroVirology
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neurocognitive disturbances associated with HIV infection may be modulated or confounded by coexisting and comorbid conditions that reflect the changing populations affected by the disease. HIV infection is often accompanied by substance dependence and/or hepatitis C co-infection. Both of these cofactors that may lead to brain dysfunction on their own, and therefore can affect the nature and course neurocognitive functioning in HIV. Improvements in antiretroviral therapies translate into greater longevity for people infected with HIV, many of whom are now entering their 6th and 7th decade of life and beyond. The increasing proportion of older persons with HIV is also the result of new infections in this age group. As aging confers additional metabolic, neurologic, and neuropsychiatric vulnerability, it is important to understand how this constellation of changes affects neurocognitive functioning in the context of HIV.
    Full-text · Article · Mar 2008 · International Review of Psychiatry
Show more