The role of oxidative stress in the pulmonary damage by influenza virus is well characterized in the mouse model. Mice infected with influenza show pulmonary damage associated with a dramatic decrease in pulmonary GSH levels as well as an increase of oxidative stress markers such as oxidized glutathione (GSSG) and lipid peroxides. 53 In these mice, oxidative stress could be due to the induction of xanthine oxidase, 54 a well-known superoxide-generating enzyme. 55 Furthermore, influenza infection is associated with an induction of inflammatory cytokines, 56,57 which might represent a likely GSH-sensitive step in its pathogenesis. Among the antioxidants shown to be protective in animal models of influenza are the xanthine oxidase inhibitor allopurinol, 54 quercetin, 58 superoxide dismutase, 59 thioredoxin, 60 NAC (alone 61 or with ribavirin 62 or oseltamavir 63 ), and GSH itself. 64 A study reported that influenza virus M2 protein augments ROS production in human airway cells in vitro, resulting in toxic effects that are prevented by the addition of GSH ester. 65 Although these studies indicate a protective role of GSH at the level of the pathogenesis of pulmonary damage, there is a report that BSO increases viral replication, 66 implying a possible antiviral role of endogenous GSH. One clinical study has shown that NAC administration improves parameters of cell-mediated immunity in patients with influenza, 66 suggesting a possible clinical relevance of these observations.