INTRATRACHEAL BUT NOT INTRAVASCULAR INTERLEUKIN-1 CAUSES ACUTE EDEMATOUS INJURY IN ISOLATED NEUTROPHIL-PERFUSED RAT LUNGS THROUGH AN OXYGENRADICAL-MEDIATED MECHANISM

Our goal was to determine whether administration of interleukin-1 (IL- 1) intratracheally causes acute edematous injury in isolated rat lungs perfused only with neutrophils and physiologic buffer. We found that administration of native (50 ng) but not heated IL-1 intratracheally r apidly (60 minutes) increased (p < 0.05) lung weights and lung ravage Ficoll concentrations in isolated rat lungs perfused only with purifie d human neutrophils as compared with lungs given IL-1 intratracheally alone, lungs perfused with neutrophils alone, or untreated control lun gs. In contrast, lung weights or lavage Ficoll concentrations did not increase (p > 0.05) when as much as 1 mu g of IL-1 was administered in travascularly with neutrophils. The mechanism of injury appeared to in volve neutrophil-derived oxygen radicals, because acute edematous inju ry did not occur in isolated lungs given IL-1 intratracheally and then perfused with neutrophils previously heated at 48 degrees C for 10 mi nutes. The latter procedure decreased superoxide anion (P-2(-)) produc tion but did not alter the adhesion or chemotactic properties of neutr ophils in vitro. In parallel, incubation with IL-1 and human neutrophi ls did not lyse (as measured by chromium 51 release) cultured purified bovine pulmonary artery endothelial cells in vitro. Our results indic ate that increased alveolar but not intravascular concentrations of IL -1 initiate a neutrophil-dependent, oxidant-mediated acute edematous l ung injury.