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Interleukin-6 limits influenza-induced inflammation and protects against fatal lung pathology

Lauder, Sarah Nicol, Jones, Emma, Smart, Kathryn, Bloom, Anja Constanze, Williams, Anwen Sian, Hindley, James P., Ondondo, Beatrice, Taylor, Philip Russel, Clement, Mathew, Fielding, Ceri Alan, Godkin, Andrew James, Jones, Simon Arnett and Gallimore, Awen Myfanwy 2013. Interleukin-6 limits influenza-induced inflammation and protects against fatal lung pathology. European Journal of Immunology 43 (10) , pp. 2613-2625. 10.1002/eji.201243018

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Abstract

Balancing the generation of immune responses capable of controlling virus replication with those causing immunopathology is critical for the survival of the host and resolution of influenza-induced inflammation. Based on the capacity of interleukin-6 (IL-6) to govern both optimal T-cell responses and inflammatory resolution, we hypothesised that IL-6 plays an important role in maintaining this balance. Comparison of innate and adaptive immune responses in influenza-infected wild-type control and IL-6-deficient mice revealed striking differences in virus clearance, lung immunopathology and generation of heterosubtypic immunity. Mice lacking IL-6 displayed a profound defect in their ability to mount an anti-viral T-cell response. Failure to adequately control virus was further associated with an enhanced infiltration of inflammatory monocytes into the lung and an elevated production of the pro-inflammatory cytokines, IFN-α and TNF-α. These events were associated with severe lung damage, characterised by profound vascular leakage and death. Our data highlight an essential role for IL-6 in orchestrating anti-viral immunity through an ability to limit inflammation, promote protective adaptive immune responses and prevent fatal immunopathology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Adaptive immunity; Heterosubtypic immunity; IL-6; Innate immunity; Pulmonary damage
Publisher: Wiley-Blackwell
ISSN: 1521-4141
Date of First Compliant Deposit: 30 March 2016
Last Modified: 16 Nov 2018 20:57
URI: http://orca.cf.ac.uk/id/eprint/58531

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Cited 18 times in Web of Science. View in Web of Science.

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