Cytokine-induced neutrophil chemoattractant is necessary for
interleukin-1-induced lung leak in rats.
Koh, Younsuck, Brooks M. Hybertson, Eric K. Jepson, Okyong J. Cho, and
John E. Repine.
Department of Internal Medicine, Asan Medical Center, University of
Ulsan School of Medicine, Seoul, Korea 138-040 and The Webb-Waring
Institute for Biomedical Research, University of Colorado Health
Sciences Center, Denver, Colorado 80262
APStracts 2:0140A, 1995.
Because interleukin-1 (IL-1) is not potent chemoattractant
intrinsically, our goal was to determine if cytokine-induced
neutrophil chemoattractant (CINC) mediates neutrophil accumulation
and leak that occurs in lungs of rats given IL-1 intratracheally. We
found that rats given IL-1 intratracheally had increased lung lavage
CINC concentrations, lung myeloperoxidase (MPO) activity, lung lavage
neutrophil numbers, and lung leak compared to saline-treated control
rats. In parallel, rats given increasing doses of anti-CINC antibody
along with IL-1 intratracheally had progressively decreased lung
lavage CINC concentrations, lung lavage neutrophil numbers, and lung
leak, but the same lung MPO activity, as rats given only IL-1
intratracheally. In addition, lavage CINC concentrations correlated
with lavage neutrophil numbers in rats. Because CINC is a
chemoattractant in vitro, and because anti-CINC antibody decreased
lung leak induced by IL-1, CINC was then given alone intratracheally.
Rats given only CINC intratracheally had the same lung MPO activity,
lung lavage neutrophil numbers, and lung leak as saline-treated
control rats. These observations suggest that instilling IL-1
intratracheally induces lung leak via a CINC-dependent pathway but
that administering CINC alone in concentrations exceeding the levels
measured in lung lavages from IL-1-treated rats is not sufficient to
cause lung neutrophil accumulation and lung leak.
Received 5 December 1994; accepted in final form 20 March 1995.
APS Manuscript Number A1237-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 April 1995.