Leukocyte-Derived Interleukin-10 Aggravates Postoperative Ileus
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 i...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02599/full |
| _version_ | 1818021931688919040 |
|---|---|
| author | Kathy Stein Mariola Lysson Beatrix Schumak Tim Vilz Sabine Specht Jürgen Heesemann Axel Roers Jörg C. Kalff Sven Wehner |
| author_facet | Kathy Stein Mariola Lysson Beatrix Schumak Tim Vilz Sabine Specht Jürgen Heesemann Axel Roers Jörg C. Kalff Sven Wehner |
| author_sort | Kathy Stein |
| collection | DOAJ |
| description | 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.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−/−, IL-10−/−, and LysMcre/IL-10fl/fl 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.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.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. |
| first_indexed | 2024-04-14T08:24:48Z |
| format | Article |
| id | doaj.art-f5e890cbcdbd43239fa716c4487c007e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T08:24:48Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f5e890cbcdbd43239fa716c4487c007e2022-12-22T02:04:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02599418867Leukocyte-Derived Interleukin-10 Aggravates Postoperative IleusKathy Stein0Mariola Lysson1Beatrix Schumak2Tim Vilz3Sabine Specht4Jürgen Heesemann5Axel Roers6Jörg C. Kalff7Sven Wehner8Department of Surgery, University of Bonn, Bonn, GermanyDepartment of Surgery, University of Bonn, Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, GermanyDepartment of Surgery, University of Bonn, Bonn, GermanyInstitute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, GermanyDepartment of Bacteriology, Max von Pettenkofer Institute, Munich, GermanyInstitute for Immunology, Medical Faculty, Technical University Dresden, Dresden, GermanyDepartment of Surgery, University of Bonn, Bonn, GermanyDepartment of Surgery, University of Bonn, Bonn, GermanyObjective: 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.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−/−, IL-10−/−, and LysMcre/IL-10fl/fl 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.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.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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02599/fullpostoperative ileusintestinal motilityinterleukin-10macrophagesneutrophils |
| spellingShingle | Kathy Stein Mariola Lysson Beatrix Schumak Tim Vilz Sabine Specht Jürgen Heesemann Axel Roers Jörg C. Kalff Sven Wehner Leukocyte-Derived Interleukin-10 Aggravates Postoperative Ileus Frontiers in Immunology postoperative ileus intestinal motility interleukin-10 macrophages neutrophils |
| title | Leukocyte-Derived Interleukin-10 Aggravates Postoperative Ileus |
| title_full | Leukocyte-Derived Interleukin-10 Aggravates Postoperative Ileus |
| title_fullStr | Leukocyte-Derived Interleukin-10 Aggravates Postoperative Ileus |
| title_full_unstemmed | Leukocyte-Derived Interleukin-10 Aggravates Postoperative Ileus |
| title_short | Leukocyte-Derived Interleukin-10 Aggravates Postoperative Ileus |
| title_sort | leukocyte derived interleukin 10 aggravates postoperative ileus |
| topic | postoperative ileus intestinal motility interleukin-10 macrophages neutrophils |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02599/full |
| work_keys_str_mv | AT kathystein leukocytederivedinterleukin10aggravatespostoperativeileus AT mariolalysson leukocytederivedinterleukin10aggravatespostoperativeileus AT beatrixschumak leukocytederivedinterleukin10aggravatespostoperativeileus AT timvilz leukocytederivedinterleukin10aggravatespostoperativeileus AT sabinespecht leukocytederivedinterleukin10aggravatespostoperativeileus AT jurgenheesemann leukocytederivedinterleukin10aggravatespostoperativeileus AT axelroers leukocytederivedinterleukin10aggravatespostoperativeileus AT jorgckalff leukocytederivedinterleukin10aggravatespostoperativeileus AT svenwehner leukocytederivedinterleukin10aggravatespostoperativeileus |