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) infection, two immunocompromising conditions that frequently coexist. This study examined the separate and combined effects of in vivo lentiviral infection and in vitro alcohol exposure on alveolar macrophage (AM) production of tumor necrosis factor- alpha (TNF-alpha), a proinflammatory cytokine that is critical to normal pulmonary host defense. AMs, recovered by bronchoalveolar lavage (BAL) from uninfected and simian immunodeficiency virus (SIV)-infected rhesus macaques, at the asymptomatic and terminal stages of infection, were cultured in ethanol 2 h prior to stimulation with lipopolysaccharide (LPS). Median TNF-alpha concentrations were measured 15 h later. Spontaneous TNF-alpha production was similar in all groups examined. LPS increased TNF-alpha 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 contrast, cells from SIV(+) asymptomatic animals had a depressed response (763 +/- 304 pg/ml). Ethanol (100 mM) suppressed the LPS-induced AM TNF-alpha response by approximately 50% in both SIV(-) and (+) animals. Ethanol-induced suppression 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 secondary infectious complications in HIV-infected hosts.
Stoltz
D A
DA
Department of Medicine, Section of Pulmonary/Critical Care, Alcohol Research Center, New Orleans, Louisiana, USA.
Nelson
S
S
Kolls
J K
JK
Zhang
P
P
Bohm
R P
RP
Murphey-Corb
M
M
Bagby
G J
GJ
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008253:Macaca mulatta; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D000914:Antibodies, Viral; D015415:Biomarkers; D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol