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>