Provocation of pulmonary vascular endothelial injury in rabbits by human recombinant interleukin-1 beta.
Interleukin-1 (IL-1) mediates components of the acute-phase response, stimulates granulocyte metabolism, and induces endothelial cell surface changes. We studied the effects of human recombinant IL-1 beta (rIL-1 beta) or rIL-1 alpha on circulating granulocytes, their sequestration within the pulmonary microvasculature, pulmonary edema formation, and changes in pulmonary vascular permeability to 125I-labeled albumin. rIL-1 beta administration induced significant (P less than 0.03) but transient granulocytopenia followed by significant (P less than 0.04) neutrophilia and significant (P less than 0.04) pulmonary leukostasis compared with saline-infused rabbits. Rabbits preinfused with 125I-labeled rabbit serum albumin and administered saline, rIL-1 beta, or rIL-1 alpha were sacrificed, and lung wet/dry weight ratios and bronchoalveolar lavage fluid and plasma 125I activities determined. Both rIL-1 beta and rIL-1 alpha increased lung wet/dry weight ratios (P less than 0.025 and P less than 0.01, respectively) compared with saline controls. rIL-1 beta increased bronchoalveolar lavage fluid/plasma 125I radioactivity ratios (P less than 0.025). Electron microscopic analysis of lung sections obtained from rIL-1 beta-infused animals demonstrated endothelial injury, perivascular edema, and extravasation of an ultrastructural permeability tracer. The observation that human rIL-1 can evoke acute pulmonary vascular endothelial injury and lung edema in rabbits supports the hypothesis that IL-1 may play a role in the pathogenesis of the adult respiratory distress syndrome.
Goldblum
S E
SE
Department of Medicine, Veterans Administration Medical Center, Baltimore, Maryland 21201.
Yoneda
K
K
Cohen
D A
DA
McClain
C J
CJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000473:pathology* / Q000648:ultrastructure; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage*; D007958:Leukocyte Count / Q000187:drug effects; D008171:Lung Diseases / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D008833:Microcirculation / Q000648:ultrastructure; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage*
D007375:Interleukin-1; D011994:Recombinant Proteins