IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis
| Autor: | Hock L. Tay, Paul S. Foster, Jay C. Horvat, Bridie J. Goggins, Steven Maltby, Philip M. Hansbro, Ellen Marks, Marjorie M. Walker, Sean W. Mateer, Michael Fricker, Kyra Minahan, Andrea Mathe, Grace Burns, Jessica Bruce, Richard Kim, Robert C. Callister, Gang Liu, Simon Keely |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chronic bronchitis Neutrophils Bacteremia Systemic inflammation Inflammatory bowel disease Pathology and Forensic Medicine Mice 03 medical and health sciences 0302 clinical medicine Pathology Animals Medicine Colitis Interleukin 6 Mice Inbred BALB C Bronchiectasis biology Interleukin-6 business.industry Dextran Sulfate Pneumonia medicine.disease Neutrophilia Mice Inbred C57BL Disease Models Animal 030104 developmental biology Immunology biology.protein Female 030211 gastroenterology & hepatology medicine.symptom business |
| Zdroj: | The American Journal of Pathology. 188:1625-1639 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2018.03.016 |
| Popis: | © 2018 American Society for Investigative Pathology Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases, such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid– and dextran sulfate sodium–induced models of colitis. Analysis of systemic inflammation identified that neutrophilia was associated with bacteremia and pyrexia in animal models of colitis. We further identified IL-6 as a systemic mediator of neutrophil recruitment from the bone marrow of dextran sulfate sodium animals. Functional inhibition of IL-6 led to reduced systemic and pulmonary neutrophilia, but it did not attenuate established colitis pathology. These data suggest that systemic bacteremia and pyrexia drive IL-6 secretion, which is a critical driver for pulmonary manifestation of IBD. Targeting IL-6 may reduce neutrophil-associated extraintestinal manifestations in IBD patients. |
| Databáze: | OpenAIRE |
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