Regulation of interleukin-1beta by interferon-gamma is species specific, limited by suppressor of cytokine signalling 1 and influences interleukin-17 production.
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.
Masters
Seth L
SL
Immunology Research Centre, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
Mielke
Lisa A
LA
Cornish
Ann L
AL
Sutton
Caroline E
CE
O'Donnell
Joanne
J
Cengia
Louise H
LH
Roberts
Andrew W
AW
Wicks
Ian P
IP
Mills
Kingston H G
KH
Croker
Ben A
BA
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
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