Phagocytes and acute lung injury: dual roles for interleukin-1.
Interleukin-1 (IL-1) and neutrophils are increased in lungs of patients with the acute respiratory distress syndrome (ARDS). We found that rats given IL-1 intratracheally rapidly developed lung neutrophil accumulation and a neutrophil-dependent acute edematous lung leak. Lung leak was associated with increased lung lavage cytokine-induced chemoattractant (CINC) levels and increased oxidative stress that was manifested by increased exhaled H2O2 levels and increased lung oxidized glutathione levels. IL-1-induced lung leak was decreased by treatment with superoxide dismutase (SOD), dimethylsulfoxide (DMSO), supercritical fluid-aerosolized vitamin E, interleukin-1-receptor antagonist (IL-1ra), or liposome-associated PGE1 (Lip-PGE1). Importantly, Lip-PGE1 treatment also reduced ventilator dependence in a small clinical study of ARDS patients. Another series of investigations revealed that IL-1 pretreatment could prevent lung leak in rats given IL-1 intratracheally. These findings point to the possible dual effects of IL-1 with respect to the development of acute lung injury.
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262, USA.
B M
BM
Hybertson
Y M
YM
Lee
J E
JE
Repine
D000527:Alprostadil / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D002630:Chemotactic Factors / Q000096:biosynthesis*; D004337:Drug Carriers; D004487:Edema / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D008954:Models, Biological; D009503:Neutropenia / Q000139:chemically induced / Q000503:physiopathology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051381:Rats; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D007507:Therapeutic Irrigation; D014747:Vinblastine
D002630:Chemotactic Factors; D004337:Drug Carriers; D007375:Interleukin-1; D008081:Liposomes; D014747:Vinblastine; D000527:Alprostadil