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

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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

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Interferons
Sepsis
Septic Shock
Myeloid Cells
Interleukin-6
Inflammation
Peritoneal Lavage
Blocking Antibodies
Ascitic Fluid
Exudates and Transudates
Endotoxins
Natural Killer Cells
Shock
Spleen
Anti-Bacterial Agents
Messenger RNA
Mortality
Liver

Keywords

  • Inflammation
  • Myeloid cells
  • Natural killer cells
  • Shock

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Romero, C. R., Herzig, D. S., Etogo, A., Nunez, J., Mahmoudizad, R., Fang, G., ... 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

The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis. / Romero, Christopher R.; Herzig, Daniela S.; Etogo, Anthony; Nunez, Jesus; Mahmoudizad, Rod; Fang, Geping; Murphey, E. D.; Toliver-Kinsky, Tracy; Sherwood, Edward R.

In: Journal of Leukocyte Biology, Vol. 88, No. 4, 10.2010, p. 725-735.

Research output: Contribution to journalArticle

Romero, CR, Herzig, DS, Etogo, A, Nunez, J, Mahmoudizad, R, Fang, G, Murphey, ED, Toliver-Kinsky, T & Sherwood, ER 2010, 'The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis', Journal of Leukocyte Biology, vol. 88, no. 4, pp. 725-735. https://doi.org/10.1189/jlb.0509307
Romero CR, Herzig DS, Etogo A, Nunez J, Mahmoudizad R, Fang G et al. The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis. Journal of Leukocyte Biology. 2010 Oct;88(4):725-735. https://doi.org/10.1189/jlb.0509307
Romero, Christopher R. ; Herzig, Daniela S. ; Etogo, Anthony ; Nunez, Jesus ; Mahmoudizad, Rod ; Fang, Geping ; Murphey, E. D. ; Toliver-Kinsky, Tracy ; Sherwood, Edward R. / The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis. In: Journal of Leukocyte Biology. 2010 ; Vol. 88, No. 4. pp. 725-735.
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