Effects of In Vitro Ethanol on Tumor Necrosis Factor-α Production by Blood Obtained From Simian Immunodeficiency Virus-Infected Rhesus Macaques.

Background: Tumor necrosis factor-α (TNF-α), a product of monocytes and macrophages, functions as an important proinflammatory cytokine in the host's response to invading pathogens. Methods: Because both alcohol abuse and human immunodeficiency virus infection affect TNF-α production and are known to frequently coexist, this study examined the effects of simian immunodeficiency virus (SIV) infection and in vitro alcohol exposure on the lipopolysaccharide (LPS)-induced TNF-α response in blood obtained from SIV-negative and -positive animals at the asymptomatic and terminal stages of infection. Results: Spontaneous TNF-α production was undetectable or low in all groups examined. LPS-induced TNF-α production was increased in blood obtained at the asymptomatic (746 ± 226 pg/ml) and terminal (1945 ± 1013 pg/ml) stages, compared with that from SIV-negative animals (210 ± 28 pg/ml), whereas TNF-α messenger RNA content did not differ in LPS-stimulated blood obtained from SIV-negative, asymptomatic SIV-positive, or terminal SIV-positive animals. Ethanol treatment suppressed TNF-α protein production in all groups, whereas TNF-α messenger RNA levels remained unchanged in blood obtained from animals not infected with SIV. Conclusions: Blood cellular elements remain responsive to LPS stimulation with respect to TNF production even into the acquired immunodeficiency syndrome stage of SIV disease. However, intoxicating doses of alcohol suppress this response, and this may contribute to the immunocompromised state of the host. [ABSTRACT FROM AUTHOR]