Alcohol abuse and smoking alter inflammatory mediator production by pulmonary and systemic immune cells

Both alcohol use disorders (AUDs) and tobacco smoking are associated with an increased predisposition for community-acquired pneumonia and the acute respiratory distress syndrome. Mechanisms are incompletely established, but may include alterations in response to pathogens by immune cells, including alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs). We sought to determine the relationship of AUDs and smoking to expression of interferon (IFN)-γ, IL-1β, IL-6, and tumor necrosis factor (TNF)-α by AMs and PBMCs from human subjects after stimulation with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA). AMs and PBMCs from healthy subjects with AUDs and controls, matched on smoking, were cultured with either LPS (1ug/mL) or LTA (5ug/mL), in the presence or absence of the antioxidant precursor N-acetylcysteine (NAC) (10mM). Cytokines were measured in cell culture supernatants. Both AMs and PBMCs expressed significantly increased IFNγ, IL-1β, IL-6, and TNFα in response to LPS and LTA. AUDs were associated with augmented pro-inflammatory cytokine production by both AMs and PBMCs in response to LPS, particularly IFNγ and IL-1β expression. Smoking diminished the impact of AUDs on AM cytokine expression. Basal AM and PBMC TLR2 and TLR4 expression was not clearly related to differences in cytokine expression; however, addition of NAC with LPS or LTA led to diminished AM and PBMC cytokine secretion, especially among current smokers. Our findings suggest that AM and PBMC immune cell responses to LPS and LTA are influenced by AUDs and smoking through mechanisms that may include alterations in cellular oxidative stress.