10.3389/fimmu.2018.02599.s005
Kathy Stein
Kathy
Stein
Mariola Lysson
Mariola
Lysson
Beatrix Schumak
Beatrix
Schumak
Tim Vilz
Tim
Vilz
Sabine Specht
Sabine
Specht
Jürgen Heesemann
Jürgen
Heesemann
Axel Roers
Axel
Roers
Jörg C. Kalff
Jörg C.
Kalff
Sven Wehner
Sven
Wehner
Table_1_Leukocyte-Derived Interleukin-10 Aggravates Postoperative Ileus.docx
Frontiers
2018
postoperative ileus
intestinal motility
interleukin-10
macrophages
neutrophils
2018-12-07 15:43:37
Dataset
https://frontiersin.figshare.com/articles/dataset/Table_1_Leukocyte-Derived_Interleukin-10_Aggravates_Postoperative_Ileus_docx/7436576
<p>Objective: Postoperative ileus (POI) is an inflammation-mediated complication of abdominal surgery, characterized by intestinal dysmotility and leukocyte infiltration into the muscularis externa (ME). Previous studies indicated that interleukin (IL)-10 is crucial for the resolution of a variety of inflammation-driven diseases. Herein, we investigated how IL-10 affects the postoperative ME inflammation and found an unforeseen role of IL-10 in POI.</p><p>Design: POI was induced by a standardized intestinal manipulation (IM) in C57BL/6 and multiple transgenic mouse strain including C-C motif chemokine receptor 2<sup>−/−</sup>, IL-10<sup>−/−</sup>, and LysM<sup>cre</sup>/IL-10<sup>fl/fl</sup> mice. Leukocyte infiltration, gene and protein expression of cytokines, chemokines, and macrophage differentiation markers as well as intestinal motility were analyzed. IL-10 serum levels in surgical patients were determined by ELISA.</p><p>Results: IL-10 serum levels were increased in patient after abdominal surgery. In mice, a complete or leucocyte-restricted IL-10 deficiency ameliorated POI and reduced the postoperative ME neutrophil infiltration. Infiltrating monocytes were identified as main IL-10 producers and undergo IL-10-dependent M2 polarization. Interestingly, M2 polarization is not crucial to POI development as abrogation of monocyte infiltration did not prevent POI due to a compensation of the IL-10 loss by resident macrophages and neutrophils. Organ culture studies demonstrated that IL-10 deficiency impeded neutrophil migration toward the surgically traumatized ME. This mechanism is mediated by reduction of neutrophil attracting chemokines.</p><p>Conclusion: Monocyte-derived macrophages are the major IL-10 source during POI. An IL-10 deficiency decreases the postoperative expression of neutrophil-recruiting chemokines, consequently reduces the neutrophil extravasation into the postsurgical bowel wall, and finally protects mice from POI.</p>