Role of interleukin 10 in murine postoperative ileus.
OBJECTIVE
Intestinal manipulation triggers an inflammatory cascade within the muscularis causing postoperative ileus (POI). The aim of this study was to investigate the recovery and therapeutic potential of interleukin 10 (IL10) for POI.


METHODS
POI was induced by bowel surgical manipulation (SM) in wild-type, IL10(-/-) and recombinant murine IL10 (rmIL10)-treated mice. Immunohistochemistry localised IL10 in the muscularis externa, histochemistry quantified neutrophil recruitment, and quantitative PCR quantified alterations in mRNA. Luminex multiplex analysis, Griess reaction and ELISA measured proteins, nitric oxide (NO) and prostanoid release from the muscularis externa, respectively, in 24 h organ culture. Gastrointestinal transit and jejunal circular muscle organ bath techniques assessed gastrointestinal function.


RESULTS
In IL10 knockouts compared with the wild type, the expression of numerous proinflammatory mRNAs (IL6, IL1 beta, chemokine C-C motif ligand 2 (CCL2) and haem oxygenase-1) and proteins (IL6, IL1 alpha, IL12, IL17, interferon gamma, tumour necrosis factor alpha, CCL2, interferon-inducible protein-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were accentuated, and release of muscle inhibitors NO and prostanoids was increased; motility never recovered from manipulation and mortality rate was 87.5%. In wild types, complete functional recovery occurred in 7 days with no mortality. SM delay in transit and suppression in jejunal circular muscle contractions were significantly improved by rmIL10 treatment. Upregulation in IL1 beta, IL6 and CCL2 mRNAs and inflammatory mediators (IL1 alpha, IL6, CCL2, macrophage inflammatory protein-1 alpha, GM-CSF, NO and prostaglandin) after SM were significantly less with rmIL10 treatment, which resulted in a decrease in neutrophil recruitment compared with SM controls.


CONCLUSIONS
IL10 plays an obligatory role in postoperative intestinal recovery, and exogenous IL10 prevents its development. Pre-emptive exogenous recombinant human IL10 could be a treatment for the prevention of clinical POI.
Department of Medicine/Gastroenterology, University of Pittsburgh, S-849 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
B
B
Stoffels
J
J
Schmidt
A
A
Nakao
A
A
Nazir
R S
RS
Chanthaphavong
A J
AJ
Bauer
D000818:Animals; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D045823:Ileus / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000502:physiology* / Q000627:therapeutic use; D007583:Jejunum / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011183:Postoperative Complications / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use
D018836:Inflammation Mediators; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10