Am. J. Respir. Crit. Care Med.,
Volume 161, Number 1, January 2000, 135-140
In Vitro Ethanol Suppresses Alveolar Macrophage TNF-
during Simian Immunodeficiency Virus Infection
DAVID A.
STOLTZ,
STEVE
NELSON,
JAY K.
KOLLS,
PING
ZHANG,
RUDOLF P.
BOHM Jr.,
MICHAEL
MURPHEY-CORB,
and
GREGORY J.
BAGBY
Department of Medicine, Section of Pulmonary/Critical Care, Department of Physiology, Alcohol Research Center, and Department of
Pediatrics, Louisiana State University Medical Center, New Orleans, Louisiana; Tulane Regional Primate Research Center, Covington,
Louisiana; and School of Medicine and Primate Center for Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania
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-
), 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-
concentrations were measured 15 h later. Spontaneous TNF-
production was similar in all groups examined.
LPS increased TNF-
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-
response by approximately 50% in both SIV(
) and (+) animals. Ethanol-induced suppression of the TNF-
response occurred at a post-transcriptional level. These data suggest that ethanol-induced suppression of the pulmonary TNF-
response may further increase the susceptibility
to and severity of secondary infectious complications in HIV-infected hosts. Stoltz DA, Nelson S,
Kolls JK, Zhang P, Bohm RP, Jr., Murphey-Corb M, Bagby GJ. In vitro ethanol suppresses alveolar macrophage TNF-
during simian immunodeficiency virus infection.