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 abnormaliti es (perivascular cuffing). These IL-1-dependent processes were inhibit ed 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 contr ibuted to lung leak. First, lung leak did not occur in rats rendered n eutropenic by vinblastine treatment 4 days before IL-1 administration but did occur in neutrophil-replete rats given vinblastine 1 day befor e IL-1 administration and control rats given IL-1. Second, treatment w ith a hydroxyl radical scavenger, dimethyl sulfoxide (DMSO) or a super oxide 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 i ncreased lung oxidized glutathione (GSSG) levels and expired H2O2 conc entrations, and these two indices of oxidative stress were decreased b y dimethyl sulfoxide or manganese superoxide dismutase treatment. We c onclude that intratracheal administration of IL-1 increases neutrophil s in the lung and causes a neutrophil and oxygen metabolite-dependent acute edematous lung injury.