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-1 alpha (IL-1) rapidly (5 h) increased leak of 125I-labeled albumin from the blood into the lung (lung leak), influx of neutrophils into lung lavages, lung 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 NAC given intravenously on lung changes following intratracheal IL-1 administration. We found that administration of NAC immediately before or 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, reduced lung GSSG increases, and decreased breath H2O2 levels in rats given IL-1 intratracheally. The latter findings are consistent with the possibility that NAC is enhancing GSH or other sulfhydryls and, as a result, reducing oxidative stress due to H2O2 or H2O2-derived products. Since postinsult treatment with NAC is effective in this relevant intact animal model of acute lung injury, we speculate that NAC may have promise in the treatment of patients with the adult respiratory distress syndrome.
Leff
J A
JA
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262.
Wilke
C P
CP
Hybertson
B M
BM
Shanley
P F
PF
Beehler
C J
CJ
Repine
J E
JE
D000111:Acetylcysteine / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood; D019803:Glutathione Disulfide; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D007375:Interleukin-1 / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011651:Pulmonary Artery; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity; D012119:Respiration; D012128:Respiratory Distress Syndrome / Q000473:pathology
D007375:Interleukin-1; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D005978:Glutathione; D019803:Glutathione Disulfide; D000111:Acetylcysteine