title: Regulation of interleukin-1beta by interferon-gamma is species specific, limited by suppressor of cytokine signalling 1 and influences interleukin-17 production.
abstract: Reports describing the effect of interferon-gamma (IFNgamma) on interleukin-1beta (IL-1beta) production are conflicting. We resolve this controversy by showing that IFNgamma potentiates IL-1beta release from human cells, but transiently inhibits the production of IL-1beta from mouse cells. Release from this inhibition is dependent on suppressor of cytokine signalling 1. IL-1beta and Th17 cells are pathogenic in mouse models for autoimmune disease, which use Mycobacterium tuberculosis (MTB), in which IFNgamma and IFNbeta are anti-inflammatory. We observed that these cytokines suppress IL-1beta production in response to MTB, resulting in a reduced number of IL-17-producing cells. In human cells, IFNgamma increased IL-1beta production, and this might explain why IFNgamma is detrimental for multiple sclerosis. In mice, IFNgamma decreased IL-1beta and subsequently IL-17, indicating that the adaptive immune response can provide a systemic, but transient, signal to limit inflammation.
authors.affiliation: Immunology Research Centre, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
authors.forename: Seth L
authors.initials: SL
authors.lastname: Masters
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Mielke
authors.forename: Ann L
authors.initials: AL
authors.lastname: Cornish
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Sutton
authors.forename: Joanne
authors.initials: J
authors.lastname: O'Donnell
authors.forename: Louise H
authors.initials: LH
authors.lastname: Cengia
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roberts
authors.forename: Ian P
authors.initials: IP
authors.lastname: Wicks
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
authors.forename: Ben A
authors.initials: BA
authors.lastname: Croker
mesh_terms: D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D020381:Interleukin-17 / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009161:Mycobacterium / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C108944:SOCS1 protein, human; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma