| First Author | Romero CR | Year | 2010 |
| Journal | J Leukoc Biol | Volume | 88 |
| Issue | 4 | Pages | 725-35 |
| PubMed ID | 20628064 | Mgi Jnum | J:165614 |
| Mgi Id | MGI:4837815 | Doi | 10.1189/jlb.0509307 |
| Citation | Romero CR, et al. (2010) The role of interferon-gamma in the pathogenesis of acute intra-abdominal sepsis. J Leukoc Biol 88(4):725-35 |
| abstractText | Several studies indicate that IFN-gamma facilitates systemic inflammation during endotoxin-induced shock. However, the pathobiology of IFN-gamma in clinically relevant models of septic shock, such as CLP, is not well understood. In this study, the role of IFN-gamma in the pathogenesis of CLP-induced septic shock was evaluated by examining IFN-gamma production at the tissue and cellular levels. The impact of IFN-gamma neutralization on systemic inflammation, bacterial clearance, and survival was also determined. Following CLP, concentrations of IFN-gamma in plasma and peritoneal lavage fluid were low in comparison with concentrations of IL-6 and MIP-2, as was IFN-gamma mRNA expression in liver and spleen. The overall percentage of IFN-gamma+ splenocytes was <5% after CLP and not statistically different from control mice. Intracellular IFN-gamma 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-gammaKO mice, and plasma concentrations of IL-6 and MIP-2 were significantly lower in IFN-gammaKO mice and in mice treated with anti-IFN-gamma compared with controls, but bacterial clearance was not affected. IFN-gammaKO mice were resistant to CLP-induced mortality when treated with systemic antibiotics. However, neutralization of IFN-gamma with blocking antibodies did not improve survival significantly. These studies show that IFN-gamma facilitates the proinflammatory response during CLP-induced septic shock. However, neutralization of IFN-gamma did not improve survival uniformly. |
