Alcohol potentiates HIV-1 infection of human blood mononuclear phagocytes.

Alcohol is one of the most commonly used and abused drugs. Chronic and acute alcohol administration is associated with alterations in specific and nonspecific immunity. Alcohol abuse significantly affects morbidity and mortality from infectious diseases. Alcohol-associated alterations in immune function include changes in cell number (Saad and Jerrells, 1991) and cytokine production (Na and Seelig, 1994). Acute or chronic alcohol consumption also modulates the function of macrophages, including the impairment of microbicidal activity and the suppression of superoxide anion production in pulmonary macrophages (D’Souza et al., 1996). Dysregulation of the production of HIV-inducing cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and IL-6 may be potential mechanisms responsible for alcohol-induced HIV infection of human immune cells. Chronic alcohol consumption, particularly alcoholic liver disease, is associated with increased levels of circulating TNF-α, IL-1, and IL-6 (Deviere et al., 1989; Khoruts et al., 1991; Lin et al., 1998; McClain and Cohen, 1989). These cytokines promote HIV replication in latently infected cells (Folks et al., 1987). Another possibility is that alcohol directly affects HIV transcription and/or activates HIV promoter long terminal repeat (LTR). Dong et al. (2000) reported that ethanol enhances TNF-α–induced activation of NF-κB and HIV LTR in CD4+ Jurkat T lymphocytes. Thus, it is reasonable to assume that alcohol acts as a cofactor for HIV infection. This hypothesis has been tested in both in vitro and in vivo model systems. Alcohol augmented HIV replication in peripheral blood mononuclear cells in vitro (Bagasra et al., 1996, 1989, 1993). In an animal model, chronic alcohol consumption accentuated the severity of murine retrovirus infection (Lee et al., 1999). Early clinical studies regarding the acceleration of HIV disease in alcohol abusers were inconclusive (MacGregor and Louria, 1997). Lake-Bakkar and Grimson (1996) reported that in a cross-sectional study of HIV disease in intravenous drug users, the relative risk of AIDS was 3.8 times higher in heavier drinkers than in moderate drinkers. Pol et al. (1996) showed that HIV-infected alcohol abusers had a 41% increase in the number of CD4 cells after cessation of alcohol use, whereas only a 15% increase was seen in uninfected control subjects who stopped consuming alcohol. Fong et al. (1994) reported a single alcoholic patient who progressed to AIDS 3 months after HIV seroconversion. Thus, this data suggested that alcohol use potentiates HIV disease progression. The mononuclear phagocyte system, which includes circulating monocytes, resident macrophages, and activated macrophages, is a major cell system in host immune and inflammatory responses. Macrophages play a central role in the immunopathogenesis of HIV disease, because they are the primary target cells for HIV infection. Monocytes/macrophages are involved in HIV infection during all stages of disease in that they serve as major target cells, reservoirs, vehicles to other tissues, and transmitters of the virus to CD4+ T cells (Levy, 1993). There is little information with respect to the effect of alcohol on HIV infection of macrophages. Thus, we examined the impact of alcohol on HIV replication in acutely infected human blood monocyte-derived macrophage (MDM). We also investigated possible mechanisms whereby alcohol exerts its effect on HIV replication in these cells.