title: Alcohol modulates alveolar macrophage tumor necrosis factor-alpha, superoxide anion, and nitric oxide secretion in the rat.
abstract: We investigated the effect of alcohol (ethanol) on the ability of the alveolar macrophage to produce tumor necrosis factor-alpha (TNF-alpha), superoxide anion (O2-), and nitric oxide (NO)--three critical components of pulmonary host defense. Male rats were treated with alcohol either acutely (priming dose 175 mg/100 g of body weight, followed by a 7-hr continuous intravenous infusion of 30 mg/100 g of body weight/hr) or chronically (12-14 weeks of feeding ethanol in a liquid diet). Three hours before sacrifice, the rats received an intravenous injection of saline or lipopolysaccharide (LPS; Escherichia coli, 026:B6, 100 micrograms/100 g of body weight). Alveolar macrophages (AMs) were then isolated by bronchoalveolar lavage and assessed for their in vitro capacity to produce TNF-alpha, O2-, and NO spontaneously and in response to different stimuli. Acute alcohol administration suppressed in vitro LPS-stimulated AM TNF-alpha secretion by 52%. AMs from both pair-and alcohol-fed rats secreted TNF-alpha spontaneously in culture. However, the AMs from chronic alcohol-fed group secreted 42-53% less TNF-alpha spontaneously and in response to LPS, interferon-gamma (IFN-gamma) or IFN-gamma + LPS compared with the AMs from pair-fed group. Systemic LPS treatment inhibited in vitro LPS-stimulated AM TNF-alpha secretion (50%) only in the control rats. Acute alcohol administration enhanced significantly in vitro phorbol 12-myristate 13-acetate (PMA)- and opsonized zymosan (OPZ)-induced AM O2- secretion (4-and 1.8-fold, respectively). Systemic LPS treatment primed the AMs from control rats to secrete 83% more O2- in response to PMA but not OPZ; however, in the acute alcohol-treated group, it suppressed both PMA (54%)- and OPZ (66%)-induced AM O2- release (loss of priming effect of LPS). Chronic alcohol feeding suppressed PMA-induced AM O2- secretion (40%) without affecting the OPZ-induced release. Although systemic LPS treatment had no significant effect on PMA or OPZ-induced AM O2- secretion in the pair-fed group, it enhanced the PMA-stimulated AM O2- release (88%) in the alcohol-fed group. AMs recovered from control or acute alcohol-treated rats did not secrete NO spontaneously in vitro. However, AMs from both pair and chronic alcohol-fed rats secreted NO spontaneously with AMs from chronic alcohol-fed group secreting 34% less. Both acute and chronic alcohol treatment inhibited AM NO secretion in response to IFN-gamma, LPS, and IFN-gamma + LPS significantly. Systemic LPS had no effect on AM NO production in response to different in vitro stimuli in any of the treatment groups. These data suggest that (1) both acute and chronic alcohol administration to rats inhibit AM TNF-alpha and NO secretion; (2) acute and chronic alcohol treatment have differential effects on AM O2- secretion; and (3) alcohol-induced alteration in AM TNF-alpha, O2-, and NO secretion may in part explain the increased susceptibility of alcohol-consuming individuals to pulmonary infections.
authors.affiliation: Department of Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
authors.forename: N B
authors.initials: NB
authors.lastname: D'Souza
authors.forename: S
authors.initials: S
authors.lastname: Nelson
authors.forename: W R
authors.initials: WR
authors.lastname: Summer
authors.forename: I V
authors.initials: IV
authors.lastname: Deaciuc
mesh_terms: D000435:Alcoholic Intoxication / Q000276:immunology*; D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D000431:Ethanol / Q000633:toxicity; D005609:Free Radicals; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D005609:Free Radicals; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D000431:Ethanol