In vitro ethanol suppresses alveolar macrophage TNF-alpha during simian immunodeficiency virus infection

Pulmonary infections are a significant cause of morbidity and mortality in patients with alcohol abuse and human immunodeficiency virus (HIV) infectio n, two immunocompromising conditions that frequently coexist. This study ex amined the separate and combined effects of in vivo lentiviral infection an d in vitro alcohol exposure on alveolar macrophage (AM) production of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine that is crit ical to normal pulmonary host defense. AMs, recovered by bronchoalveolar la vage (BAL) from uninfected and simian immunodeficiency virus (SIV)-infected rhesus macaques, at the asymptomatic and terminal stages of infection, wer e cultured in ethanol 2 h prior to stimulation with lipopolysaccharide (LPS ). Median TNF-alpha concentrations were measured 15 h later. Spontaneous TN F-alpha production was similar in all groups examined. LPS increased TNF-al pha protein production similarly in SIV(-) (2,381 +/-. 359 pg/ml) and SIV() animals at the terminal stage of infection (2,019 +/- 507 pg/ml). In cont rast, cells from SIV(+) asymptomatic animals had a depressed response (763 +/- 304 pg/ml). Ethanol (100 mM) suppressed the LPS-induced AM INF-a respon se by approximately 50% in both SIV(-) and (+) animals. Ethanol-induced sup pression of the TNF-alpha response occurred at a post-transcriptional level . These data suggest that ethanol-induced suppression of the pulmonary TNF- alpha response may further increase the susceptibility to and severity of s econdary infectious complications in HIV-infected hosts.