IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3
- Author(s)
- Croker, BA; Kiu, H; Pellegrini, M; Toe, J; Preston, S; Metcalf, D; O'Donnell, JA; Cengia, LH; McArthur, K; Nicola, NA; Alexander, WS; Roberts, AW;
- Details
- Publication Year 2012-01,Volume 90,Issue #1,Page 124-129
- Journal Title
- IMMUNOLOGY AND CELL BIOLOGY
- Publication Type
- Journal Article
- Abstract
- The lack of expression of the suppressor of cytokine signalling-3 (SOCS3) or inactivation of the negative regulatory capacity of SOCS3 has been well documented in rheumatoid arthritis, viral hepatitis and cancer. The specific qualitative and quantitative consequences of SOCS3 deficiency on interleukin-6 (IL-6)-mediated pro-and anti-inflammatory responses remain controversial in vitro and unknown in vivo. Mice with a conditional deletion of SOCS3 in hematopoietic cells develop lethal inflammatory disease during adult life and develop gross histopathological changes during experimental arthritis, typified by elevated IL-6 levels. To clarify the nature of the IL-6 responses in vivo, we generated mice deficient in SOCS3 (SOCS3(-/Delta vav)) or both SOCS3 and IL-6 (IL-6(-/-)/SOCS3(-/Delta vav)), and examined responses in models of acute and chronic inflammation. Acute responses to IL-1 beta were lethal to SOCS3(-/Delta vav) mice but not IL-6(-/-)/SOCS3(-/Delta vav) mice, indicating that IL-6 was required for the lethal inflammation induced by IL-1 beta. Administration of IL-1 beta to SOCS3(-/Delta vav) mice induced systemic apoptosis of lymphocytes in the thymus, spleen and lymph nodes that was dependent on the presence of IL-6. IL-6 deficiency prolonged survival of SOCS3(-/Delta vav) mice and ameliorated spontaneous inflammatory disease developing during adult life. Infection of SOCS3(-/Delta vav) mice with LCMV induced a lethal inflammatory response that was dependent on IL-6, despite SOCS3(-/Delta vav) mice controlling viral replication. We conclude that SOCS3 is required for survival during inflammatory responses and is a critical regulator of IL-6 in vivo. Immunology and Cell Biology (2012) 90, 124-129; doi: 10.1038/icb.2011.29; published online 26 April 2011
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- LYMPHOCYTIC CHORIOMENINGITIS VIRUS; INTERLEUKIN-6-DEFICIENT MICE; IN-VIVO; ANTIINFLAMMATORY CYTOKINE; AUTOIMMUNE MYOCARDITIS; IL-6-DEFICIENT MICE; INDUCED ARTHRITIS; DOUBLE-BLIND; RESPONSES; RECEPTOR
- Research Division(s)
- Infection And Immunity; Cancer And Haematology; Inflammation
- Publisher's Version
- https://doi.org/10.1038/icb.2011.29
- Open Access at Publisher's Site
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146962/- Terms of Use/Rights Notice
- © 2013 Australasian Society for Immunology
Creation Date: 2012-01-01 12:00:00