title: Interleukin-6 limits influenza-induced inflammation and protects against fatal lung pathology.
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.
authors.affiliation: Cardiff Institute of Infection and Immunity, School of Medicine, Cardiff University, Heath Park, Cardiff, UK.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Lauder
authors.forename: Emma
authors.initials: E
authors.lastname: Jones
authors.forename: Kathryn
authors.initials: K
authors.lastname: Smart
authors.forename: Anja
authors.initials: A
authors.lastname: Bloom
authors.forename: Anwen S
authors.initials: AS
authors.lastname: Williams
authors.forename: James P
authors.initials: JP
authors.lastname: Hindley
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ondondo
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Mathew
authors.initials: M
authors.lastname: Clement
authors.forename: Ceri
authors.initials: C
authors.lastname: Fielding
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Godkin
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.forename: Awen M
authors.initials: AM
authors.lastname: Gallimore
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D009980:Influenza A virus / Q000502:physiology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology*; D011024:Pneumonia, Viral / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D019562:Viral Load / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6
keywords: Adaptive immunity · Heterosubtypic immunity · IL-6 · Innate immunity · Pulmonary damage