Alcohol modulates alveolar macrophage tumor necrosis factor-alpha, superoxide anion, and nitric oxide secretion in the rat

We investigated the effect of alcohol (ethanol) on the ability of the alveolar macrophage to produce tumor necrosis factor-alpha (TNF-alpha), superoxide anion (O-2(-)), 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 mu g/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, O-2(-), 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 O-2(-) secretion (4- and 1.8-fold, respectively), Systemic LPS treatment primed the AMs from control rats to secrete 83% more O-2(-) in response to PMA but not OPZ; however, in the acute alcohol-treated group, it suppressed both PMA (54%)- and OPZ (66%)-induced AM O-2(-) release (loss of priming effect of LPS). Chronic alcohol feeding suppressed PMA-induced AM O-2(-) secretion (40%) without affecting the OPZ-induced release. Although systemic LPS treatment had no significant effect on PMA or OPZ-induced AM O-2(-) secretion in the pair-fed group, it enhanced the PMA-stimulated AM O-2(-) 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, LF'S, 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 O-2(-) secretion; and (3) alcohol-induced alteration in AM TNF-alpha, O-2(-), and NO secretion may in part explain the increased susceptibility of alcohol-consuming individuals to pulmonary infections.