[HTML][HTML] IL-6 drives neutrophil-mediated pulmonary inflammation associated with bacteremia in murine models of colitis

SW Mateer, A Mathe, J Bruce, G Liu, S Maltby… - The American journal of …, 2018 - Elsevier
SW Mateer, A Mathe, J Bruce, G Liu, S Maltby, M Fricker, BJ Goggins, HL Tay, E Marks
The American journal of pathology, 2018Elsevier
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 …
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.
Elsevier