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.


OBJECTIVE
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 alpha 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 NH(2) 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.
Zingarelli
B
B
Children's Hospital Medical Center, Division of Critical Care, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. bzingarelli@chmcc.org
Yang
Z
Z
Hake
P W
PW
Denenberg
A
A
Wong
H R
HR
D000210:Acute-Phase Reaction / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D016753:Interleukin-10 / Q000172:deficiency*; D015850:Interleukin-6 / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D008315:Malondialdehyde / Q000494:pharmacology; D008643:Mesentery / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D020556:Neutrophil Infiltration / Q000502:physiology; D019007:P-Selectin / Q000502:physiology; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D012720:Severity of Illness Index; D013152:Splanchnic Circulation / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
D015850:Interleukin-6; D019007:P-Selectin; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D008315:Malondialdehyde; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases