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, J. H. Williams

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

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 ~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 ~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.

Original languageEnglish (US)
Pages (from-to)L245-L250
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume268
Issue number2 12-2
DOIs
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Ulich, T. R., Howard, S. C., Remick, D. G., Wittwer, A., Yi, E. S., Yin, S., Guo, K., Welply, J. K., & Williams, J. H. (1995). Intratracheal administration of endotoxin and cytokines. VI. Antiserum to CINC inhibits acute inflammation. American Journal of Physiology - Lung Cellular and Molecular Physiology, 268(2 12-2), L245-L250. https://doi.org/10.1152/ajplung.1995.268.2.l245