In summary, we determined that zinc supplementation of alcohol-fed rats improves PU.1 and Nrf2 nuclear binding in the alveolar macrophage, reverses alcohol-induced redox imbalance, and enhances lung bacterial clearance in an experimental pneumonia model. These findings provide compelling evidence that zinc deficiency interferes with both GM-CSF-dependent immune function and ARE-mediated antioxidant defenses, and thereby contribute to the alcoholic lung phenotype. Clinically, alcohol abusers are more susceptible to pneumonia and are more likely to develop acute lung injury in response to pneumonia and/or other acute insults. It is intriguing to postulate that zinc deficiency plays an important role in the defective immune and antioxidant defenses in this population. Even more exciting is the possibility that dietary zinc supplementation could be a simple and safe intervention that could improve the health of these vulnerable individuals.
