AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 245-L250, Copyright © 1995 by American Physiological Society
Intratracheal administration of endotoxin and cytokines. VI. Antiserum to CINC inhibits acute inflammation
T. R. Ulich, S. C. Howard, D. G. Remick, A. Wittwer, E. S. Yi, S. Yin, K. Guo, J. K. Welply and J. H. Williams
Department of Pathology, University of California San Diego School of Medicine 92103.
Cytokine-induced neutrophil chemoattractant (CINC), a chemotactic molecule
of the interleukin (IL)-8 family, is known to be induced in the rat in
response to tumor necrosis factor (TNF), IL-1, and lipopolysaccharide
(LPS). Intratracheal injection of endotoxin (LPS) is shown to cause CINC
mRNA expression in pulmonary tissue, peaking after 2 h, and CINC protein
expression in bronchoalveolar lavage (BAL) fluid, peaking after 2-4 h.
Intratracheal injection of synthetic CINC causes acute inflammation that is
abrogated by coinjection of antiserum to purified natural rat CINC.
Intratracheal injection of antiserum to CINC inhibits intratracheal LPS-
and IL-1-induced neutrophil emigration into BAL fluid by approximately
60-70%. Despite the anti-inflammatory activity of anti-CINC antiserum, TNF
is elevated in the lavage fluid of rats receiving anti-CINC, suggesting
that CINC may act in a negative feedback loop to downregulate TNF
expression. Intratracheal injection of antiserum to CINC combined with
intravenous injection of anti-E-selectin antibody inhibits intratracheal
LPS- and IL-1-induced neutrophil emigration into BAL fluid by approximately
75-85%. CINC-mediated chemotactic activity and E-selectin-mediated
adherence of neutrophils to endothelium contribute significantly to the
pathogenesis of LPS-initiated acute inflammation.
