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Absence of endogenous interleukin 10 enhances early stress response during post-ischaemic injury in mice intestine


BACKGROUND Interleukin 10 (IL-10) exerts a wide spectrum of regulatory activities in immune and inflammatory responses.

AIMS The aim of this study was to investigate the role of endogenous IL-10 on modulation of the early inflammatory response after splanchnic ischaemia and reperfusion.

METHODS Intestinal damage was induced by clamping the superior mesenteric artery and the coeliac trunk for 45 minutes followed by reperfusion in IL-10 deficient mice (IL-10−/−) and wild-type controls.

RESULTS IL-10−/−mice experienced a higher rate of mortality and more severe tissue injury compared with wild-type mice subjected to ischaemia and reperfusion. Splanchnic injury was characterised by massive epithelial haemorrhagic necrosis, upregulation of P-selectin and intercellular adhesion molecule 1, and neutrophil infiltration. The degree of oxidative and nitrosative damage was significantly higher in IL-10−/− mice than in wild-type littermates, as indicated by elevated malondialdehyde levels and formation of nitrotyrosine. Plasma levels of the proinflammatory cytokines tumour necrosis factor α and interleukin 6 were also greatly enhanced in comparison with wild-type mice. These events were preceded by increased immunostaining and activity of the stress regulated c-Jun NH2 terminal kinase and activation of the transcription factor activator protein 1 in the cellular nuclei of damaged tissue.

CONCLUSIONS These data demonstrate that endogenous IL-10 exerts an anti-inflammatory role during reperfusion injury, possibly by regulating early stress related genetic response, adhesion molecule expression, neutrophil recruitment, and subsequent cytokine and oxidant generation.

  • splanchnic tissue
  • activator protein 1
  • adhesion molecules
  • interleukin 6
  • c-Jun NH2 terminal kinase
  • tumour necrosis factor α
  • Abbreviations used in this paper

    activator protein 1
    intercellular adhesion molecule 1
    interleukin 6
    interleukin 10
    c-Jun NH2 terminal kinase
    tumour necrosis factor α
    electrophoretic mobility shift assays
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