Interleukin-1-induced lung neutrophil accumulation and oxygen metabolite-mediated lung leak in rats.
We found that intratracheal administration of recombinant interleukin-1 alpha (IL-1) into rats rapidly (< 5 h) increased neutrophils in lung lavages and caused an acute edematous lung injury which was reflected by lung albumin accumulation (lung leak) and histological abnormalities (perivascular cuffing). These IL-1-dependent processes were inhibited by prior administration of recombinant IL-1 receptor antagonist and did not occur following administration of heated IL-1. Several lines of evidence suggested that neutrophil-derived oxygen metabolites contributed to lung leak. First, lung leak did not occur in rats rendered neutropenic by vinblastine treatment 4 days before IL-1 administration but did occur in neutrophil-replete rats given vinblastine 1 day before IL-1 administration and control rats given IL-1. Second, treatment with a hydroxyl radical scavenger, dimethyl sulfoxide (DMSO) or a superoxide anion scavenger, manganese superoxide dismutase, decreased lung leak, lung lavage neutrophils, and histological abnormalities in rats given IL-1 intratracheally. Third, intratracheal IL-1 administration increased lung oxidized glutathione (GSSG) levels and expired H2O2 concentrations, and these two indices of oxidative stress were decreased by dimethyl sulfoxide or manganese superoxide dismutase treatment. We conclude that intratracheal administration of IL-1 increases neutrophils in the lung and causes a neutrophil and oxygen metabolite-dependent acute edematous lung injury.
Leff
J A
JA
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262.
Baer
J W
JW
Bodman
M E
ME
Kirkman
J M
JM
Shanley
P F
PF
Patton
L M
LM
Beehler
C J
CJ
McCord
J M
JM
Repine
J E
JE
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D006861:Hydrogen Peroxide; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology*; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000473:pathology*; D009994:Osmolar Concentration; D010100:Oxygen / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D013482:Superoxide Dismutase / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
D007375:Interleukin-1; D014747:Vinblastine; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D005978:Glutathione; D010100:Oxygen; D019803:Glutathione Disulfide; D004121:Dimethyl Sulfoxide