Interleukin-23: A key cytokine in inflammatory diseases

被引:230
作者
Duvallet, Emilie
Semerano, Luca
Assier, Eric
Falgarone, Geraldine
Boissier, Marie-Christophe
机构
[1] Univ Paris 13, EA4222, F-93000 Bobigny, France
[2] Grp Hosp Avicenne Jean Verdier Rene Muret, AP HP, Serv Rhumatol, F-93000 Bobigny, France
关键词
Cytokines; interleukin-23; rheumatoid arthritis; spondyloarthritis; T cells; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; TGF-BETA; T-CELLS; USTEKINUMAB; RECEPTOR; IL-23; ARTHRITIS; TRIAL;
D O I
10.3109/07853890.2011.577093
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Interleukin-23 (IL-23) is a pro-inflammatory cytokine composed of two subunits, p19 and p40. The p40 subunit is shared with IL-12. IL-23 and IL-12 have different receptors and different effects. Whereas IL-12 induces development of Th1 cells, which produce interferon-gamma, IL-23 is involved in differentiation of Th17 cells in a pro-inflammatory context and especially in the presence of TGF-beta and IL-6. Activated Th17 cells produce IL-17A, IL-17F, IL-6, IL-22, TNF-alpha, and GM-CSF. Inflammatory macrophages express IL-23R and are activated by IL-23 to produce IL-1, TNF-alpha, and IL-23 itself. These effects identify IL-23 as a central cytokine in autoimmunity and a highly promising treatment target for inflammatory diseases. IL-23 is found in the skin of patients with psoriasis, in the bowel wall of patients with chronic inflammatory bowel disease, and in synovial membrane of patients with rheumatoid arthritis. IL-23 is involved in osteoclastogenesis, independently from IL-17, via induction of RANKL expression. Debate continues to surround the role for IL-23 in the pathophysiology of inflammatory joint diseases (rheumatoid arthritis and spondyloarthritis). Ustekinumab, which inhibits IL-12 and IL-23 by blocking p40, has been found effective in cutaneous psoriasis and psoriatic arthritis, as well as in Crohn's disease. Treatments that specifically target IL-23 (antibodies to p19) are being developed.
引用
收藏
页码:503 / 511
页数:9
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