Effects of ethanol on cytokine generation and NFκB activity in human lung epithelial cell

Alcohol abuse is associated with enhanced risk for pulmonary infections, but the mechanisms remain obscure. We assessed whether ethanol reduced generation of cytokines from a human lung epithelial cell line (A549) in vitro and if effects on the NFκB transcription factor were involved. Exposure of A549 to ethanol (0.1-1%) dose-dependently inhibited (by 15-49%) the release of G-CSF and IL-8, but not of M-CSF, triggered by IL1β or TNFα. Ethanol also inhibited by 49% the IL-1β stimulated translocation of the p65 subunit of NFκB from the cytoplasm into the nucleus. Using a κB binding and luciferase coupled construct, transfected into A549 cells, we found that 1% ethanol specifically reduced IL-1β and TNFα induced luciferase activity with 34 and 40%, respectively. Thus, in vitro exposure of lung epithelial cells to ethanol reduced the generation of cytokines, as well as translocation and gene activation by NFκB.