Intratracheal but not intravascular interleukin-1 causes acute edematous injury in isolated neutrophil-perfused rat lungs through an oxygen radical-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 rapidly (60 minutes) increased (p < 0.05) lung weights and lung lavage Ficoll concentrations in isolated rat lungs perfused only with purified human neutrophils as compared with lungs given IL-1 intratracheally alone, lungs perfused with neutrophils alone, or untreated control lungs. In contrast, lung weights or lavage Ficoll concentrations did not increase (p > 0.05) when as much as 1 microgram of IL-1 was administered intravascularly with neutrophils. The mechanism of injury appeared to involve neutrophil-derived oxygen radicals, because acute edematous injury did not occur in isolated lungs given IL-1 intratracheally and then perfused with neutrophils previously heated at 48 degrees C for 10 minutes. The latter procedure decreased superoxide anion (O2-.) production but did not alter the adhesion or chemotactic properties of neutrophils in vitro. In parallel, incubation with IL-1 and human neutrophils did not lyse (as measured by chromium 51 release) cultured purified bovine pulmonary artery endothelial cells in vitro. Our results indicate that increased alveolar but not intravascular concentrations of IL-1 initiate a neutrophil-dependent, oxidant-mediated acute edematous lung injury.
Guidot
D M
DM
Webb-Waring Institute for Biomedical Research, Denver, CO.
Stevens
E E
EE
Repine
M J
MJ
Lucca-Broco
A E
AE
Repine
J E
JE
D000208:Acute Disease; D000818:Animals; D005362:Ficoll; D005609:Free Radicals; D006358:Hot Temperature; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000008:administration & dosage / Q000502:physiology* / Q000633:toxicity; D007442:Intubation, Intratracheal; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009929:Organ Size; D010477:Perfusion; D011654:Pulmonary Edema / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D005609:Free Radicals; D007375:Interleukin-1; D017382:Reactive Oxygen Species; D005362:Ficoll