POSTINSULT TREATMENT WITH N-ACETYL-L-CYSTEINE DECREASES IL-1-INDUCED NEUTROPHIL INFLUX AND LUNG LEAK IN RATS

We found that intratracheal administration of interleukin-lalpha (IL-1 ) rapidly (5 h) increased leak of I-125-labeled albumin from the blood into the lung (lung leak), influx of neutrophils into lung lavages, l ung oxidized glutathione (GSSG) levels, breath hydrogen peroxide (H2O2 ) concentrations, and lung histological abnormalities in intact rats. Since N-acetyl-L-cysteine (NAC) increases glutathione (GSH) levels in vivo and scavenges oxygen radicals in vitro, we tested the effect of N AC given intravenously on lung changes following intratracheal IL-1 ad ministration. We found that administration of NAC immediately before o r 2.5 h after intratracheal administration of IL-1 decreased lung leak , neutrophil influx into lung lavages, and defects in lung histology. NAC treatment also increased blood acid soluble sulfhydryl levels, red uced lung GSSG increases, and decreased breath H2O2 levels in rats giv en IL-1 intratracheally. The latter findings are consistent with the p ossibility that NAC is enhancing GSH or other sulfhydryls and, as a re sult, reducing oxidative stress due to H2O2 or H2O2-derived products. Since postinsult treatment with NAC is effective in this relevant inta ct animal model of acute lung injury, we speculate that NAC may have p romise in the treatment of patients with the adult respiratory distres s syndrome.