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 ORCID: https://orcid.org/0000-0001-6118-020X, Hindley, James P., Ondondo, Beatrice, Taylor, Philip Russel ORCID: https://orcid.org/0000-0003-0163-1421, Clement, Mathew ORCID: https://orcid.org/0000-0002-9280-5281, Fielding, Ceri Alan ORCID: https://orcid.org/0000-0002-5817-3153, Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567, Jones, Simon Arnett ORCID: https://orcid.org/0000-0001-7297-9711 and Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004 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:	11 Oct 2023 18:21
URI:	https://orca.cardiff.ac.uk/id/eprint/58531

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