Journal of Applied Physiology
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J Appl Physiol 63: 2093-2100, 1987;
8750-7587/87 $5.00
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Journal of Applied Physiology, Vol 63, Issue 5 2093-2100, Copyright © 1987 by American Physiological Society

ARTICLES

Monokine-induced acute lung injury in rabbits

S. E. Goldblum, M. Jay, K. Yoneda, D. A. Cohen, C. J. McClain and M. N. Gillespie
Department of Medicine, Veterans Administration Medical Center, Lexington, Kentucky.

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.


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