IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis

Mateer, SW; Mathe, A; Bruce, J; Liu, G; Maltby, S; Fricker, M; Goggins, BJ; Tay, HL; Marks, E; Burns, G; Kim, RY; Minahan, K; Walker, MM; Callister, RC; Foster, PS; Horvat, JC; Hansbro, PM; Keely, S

IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis

Mateer, SW Mathe, A Bruce, J Liu, G

Maltby, S Fricker, M Goggins, BJ Tay, HL Marks, E Burns, G Kim, RY

Minahan, K Walker, MM Callister, RC Foster, PS Horvat, JC Hansbro, PM

Keely, S

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Publication Type:: Journal Article
Citation:: American Journal of Pathology, 2018, 188 (7), pp. 1625 - 1639
Issue Date:: 2018-07-01

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Field	Value	Language
dc.contributor.author	Mateer, SW	en_US
dc.contributor.author	Mathe, A	en_US
dc.contributor.author	Bruce, J	en_US
dc.contributor.author	Liu, G https://orcid.org/0000-0002-0489-2638	en_US
dc.contributor.author	Maltby, S	en_US
dc.contributor.author	Fricker, M	en_US
dc.contributor.author	Goggins, BJ	en_US
dc.contributor.author	Tay, HL	en_US
dc.contributor.author	Marks, E	en_US
dc.contributor.author	Burns, G	en_US
dc.contributor.author	Kim, RY https://orcid.org/0000-0002-8709-5270	en_US
dc.contributor.author	Minahan, K	en_US
dc.contributor.author	Walker, MM	en_US
dc.contributor.author	Callister, RC	en_US
dc.contributor.author	Foster, PS	en_US
dc.contributor.author	Horvat, JC	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Keely, S	en_US
dc.date.available	2018-03-23	en_US
dc.date.issued	2018-07-01	en_US
dc.identifier.citation	American Journal of Pathology, 2018, 188 (7), pp. 1625 - 1639	en_US
dc.identifier.issn	0002-9440	en_US
dc.identifier.uri	http://hdl.handle.net/10453/134015
dc.description.abstract	© 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.	en_US
dc.relation.ispartof	American Journal of Pathology	en_US
dc.relation.isbasedon	10.1016/j.ajpath.2018.03.016	en_US
dc.subject.classification	Pathology	en_US
dc.subject.mesh	Neutrophils	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Bacteremia	en_US
dc.subject.mesh	Colitis	en_US
dc.subject.mesh	Pneumonia	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Dextran Sulfate	en_US
dc.subject.mesh	Interleukin-6	en_US
dc.subject.mesh	Female	en_US
dc.title	IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis	en_US
dc.type	Journal Article
utslib.citation.volume	7	en_US
utslib.citation.volume	188	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	7	en_US
pubs.publication-status	Published	en_US
pubs.volume	188	en_US

Abstract:

© 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.

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http://hdl.handle.net/10453/134015