Alcoholism is a well known predisposition for severe bacterial pneumonia. Ethanol causes suppression of selected polymorphonuclear leukocyte (PMN) functions and has a particularly severe impact on antibacterial defenses against gram-negative organisms. Although the mechanisms for these anti-inflammatory efects are unknown, they may relate to cellular membrane perturbation and subsequent alterations in intracellular cyclic nucleotide levels. We will use a rat model to achieve the following specific aims: 1) describe in vivo pulmonary antibacterial defenses against a clinically relevant microorganism under varying conditions of acute and chronic ethanol consumption. 2) evaluate the in vivo recruitment, phagocytosis and intracellular killing activity of PMNs and alveolar macrophages in response to intrapulmonary bacteria during acute and chronic alcohol consumption. 3) assess beta-receptor binding characteristics and measure cAMP accumulation following stimulation of beta-receptors and adenyl cyclase in PMNs isolated from acute and chronic alcoholic animals. 4) determine the effects of ethanol on bacterial adherence to tracheal tissue, intratracheal bacterial clearance and spontaneous alteration of normal tracheal flora. Intrapulmonary and intratracheal clearance will be quantitated following aerosol exposure of radiolabeled bacteria to animals acutely intoxicated or chronically fed an ethanol diet. PMN and alveolar macrophage mobilization, phagocytosis and intracellular killing activities will be assessed in vivo and in the same lung in which intrapulmonary clearance was measured. We will also quantitate cyclic AMP metabolism in PMN isolated from alcoholic animals to assess the role of cyclic nucleotides in mediating the anti-inflammatory effects of ethanol. Analysis of these results will contribute to our understanding of the known impairment in host defenses that accompany alcohol abuse.
