Monokine-induced acute lung injury in rabbits.
Interleukin-1 (IL-1) mediates components of the acute phase response, stimulates granulocyte metabolism, and induces endothelial cell surface changes. We studied in unanesthetized rabbits the effects of intravenous divided dose infusions of a murine monokine preparation containing IL-1 activity, on circulating granulocytes, their sequestration within the pulmonary microvasculature, pulmonary edema formation, and changes in pulmonary vascular permeability. Monokine administration induced significant (P less than 0.01) granulocytopenia as well as a significant (P less than 0.001) increase in mean alveolar septal wall granulocytes per high power field (HPF) compared with saline-injected controls. Infusions of the monokine preparation significantly (P less than 0.005) increased lung wet-to-dry weight ratios as well as significantly (P less than 0.025) increased pulmonary extravasation of radiolabeled albumin. Electron microscopic analysis of lung sections obtained from monokine-infused animals demonstrated endothelial injury, perivascular edema, and extravasation of an ultrastructural tracer. We conclude that a monokine preparation containing IL-1 activity can induce profound granulocytopenia, pulmonary leukostasis, and acute pulmonary vascular endothelial injury.
D000380:Agranulocytosis / Q000139:chemically induced*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D006098:Granulocytes; D007375:Interleukin-1 / Q000633:toxicity*; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology; D011654:Pulmonary Edema / Q000139:chemically induced*; D011817:Rabbits
D007375:Interleukin-1