The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis

Christopher R. Romero, Daniela S. Herzig, Anthony Etogo, Jesus Nunez, Rod Mahmoudizad, Geping Fang, E. D. Murphey, Tracy Toliver-Kinsky, Edward R. Sherwood

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Several studies indicate that IFN-γ facilitates systemic inflammation during endotoxin-induced shock. However, the pathobiology of IFN-γ in clinically relevant models of septic shock, such as CLP, is not well understood. In this study, the role of IFN-γ in the pathogenesis of CLP-induced septic shock was evaluated by examining IFN-γ production at the tissue and cellular levels. The impact of IFN-γ neutralization on systemic inflammation, bacterial clearance, and survival was also determined. Following CLP, concentrations of IFN-γ in plasma and peritoneal lavage fluid were low in comparison with concentrations of IL-6 and MIP-2, as was IFN-γ mRNA expression in liver and spleen. The overall percentage of IFN- γ+ splenocytes was <5% after CLP and not statistically different from control mice. Intracellular IFN-γ was present in a large proportion of peritoneal exudate cells after CLP, primarily in infiltrating myeloid cells and NK cells. i.p. myeloid cell activation was decreased in IFN-γKO mice, and plasma concentrations of IL-6 and MIP-2 were significantly lower in IFN-γKO mice and in mice treated with anti-IFN-γ compared with controls, but bacterial clearance was not affected. IFN-γKO mice were resistant to CLP-induced mortality when treated with systemic antibiotics. However, neutralization of IFN-γ with blocking antibodies did not improve survival significantly. These studies show that IFN-γ facilitates the proinflammatory response during CLP-induced septic shock. However, neutralization of IFN-γ did not improve survival uniformly.

Original languageEnglish (US)
Pages (from-to)725-735
Number of pages11
JournalJournal of Leukocyte Biology
Volume88
Issue number4
DOIs
StatePublished - Oct 2010

Keywords

  • Inflammation
  • Myeloid cells
  • Natural killer cells
  • Shock

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    Romero, C. R., Herzig, D. S., Etogo, A., Nunez, J., Mahmoudizad, R., Fang, G., Murphey, E. D., Toliver-Kinsky, T., & Sherwood, E. R. (2010). The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis. Journal of Leukocyte Biology, 88(4), 725-735. https://doi.org/10.1189/jlb.0509307