Chemokine C10 promotes disease resolution and survival in an experimental model of bacterial sepsis

M. L. Steinhauser, C. M. Hogaboam, A. Matsukawa, N. W. Lukacs, R. M. Strieter, S. L. Kunkel

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Previous studies have suggested that the C-C chemokine C10 is involved in the chronic stages of host defense reactions. The present study addressed the role of C10 in a murine model of septic peritonitis, induced by cecal ligation and puncture (CLP). Unlike other C-C chemokines, C10 levels in the peritoneal wash were increased approximately 30-fold above baseline levels at 48 h after CLP surgery. Immunoneutralization of peritoneal C10 levels with polyclonal anti-C10 antiserum during CLP-induced peritonitis negatively impacted mouse survival over 4 days. In contrast, when 500 ng of recombinant murine C10 was administered immediately after CLP surgery, the 4-day survival rate increased from 20% to over 60%. The C10 therapy appeared to facilitate a rapid and significant enhancement of the levels of tumor necrosis factor alpha (TNF-α) and monocyte chemoattracrant protein-1 (MCP-1) and a later increase in interieukin-13 (IL-13) levels in the peritoneal cavity. In vitro studies showed that the combination of IL-1β and C10 markedly augmented TNF-α synthesis by peritoneal macrophages and that C10 synthesis was induced in these cells following their exposure to IL-13. At 24 h after CLP surgery, only 25% of C10-treated mice were bacteremic versus 85% of the control group that exhibited dissemination of bacteria into the circulation. The lack of bacteremia in C10-treated mice appeared to be related, in part, to in vitro evidence flint C10 significantly enhanced the bacterial phagocytic activity of peritoneal macrophages. In addition, in vivo evidence suggested that C10 therapy significanfly reduced the amount of material that leaked from the damaged gut. Taken together, the results of this study demonstrate that the C10 chemokine rapidly promotes disease resolution in the CLP model through its direct effects on the cellular events critically involved in host defense during septic peritonitis.

Original languageEnglish
Pages (from-to)6108-6114
Number of pages7
JournalInfection and Immunity
Volume68
Issue number11
DOIs
Publication statusPublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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