IL-10 is not protective in intestinal ischemia reperfusion injury.
BACKGROUND
Ischemia/reperfusion of the small intestine disrupts gut barrier function, increases bacterial translocation, and activates systemic pro-inflammatory responses. Pharmacological treatment with the anti-inflammatory cytokine interleukin-10 (IL-10) following ischemia to muscle reduces the severity of local and systemic inflammation. While endogenous IL-10 is protective in murine models of acute endotoxemia, its physiological role during direct gut injury is unknown.


METHODS
Mice genetically deficient in IL-10 (IL-10(-/-)) and their normal littermates (IL-10(+/+)) underwent 20 to 50 min of gut ischemia by occlusion of the superior mesenteric artery.


RESULTS
Both short- and long-term (>16 h) survival after reperfusion of IL-10(-/-) mice was identical to that of the wild-type littermates, with 50% mortality observed at 35 min of occlusion. The small bowel demonstrated discrete gross areas of hemorrhage and ischemia localized to the jejunum. No significant difference in the extent or time for occurrence of macroscopic or microscopic intestinal damage to the small bowel was observed in IL-10(-/-) or IL-10(+/+) mice, despite the marked elevation in serum IL-6.


CONCLUSIONS
The absolute serum concentration of IL-6 in the presence or the absence of IL-10 does not affect local or systemic response to ischemic intestinal injury. These results also demonstrate that the anti-inflammatory cytokine IL-10 does not play a significant local or systemic protective role in this model of ischemia/reperfusion.
Stallion
Anthony
A
Department of Pediatric Surgery, Case Western Reserve University School of Medicine and Cleveland Clinic Children's Hospital, Cleveland, Ohio 44106-4952, USA.
Kou
Tzuyung D
TD
Miller
Kelly A
KA
Dahms
Beverly B
BB
Dudgeon
David L
DL
Levine
Alan D
AD
D000818:Animals; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D007583:Jejunum / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009994:Osmolar Concentration; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index
D015850:Interleukin-6; D016753:Interleukin-10