This review describes the IL-20 family of cytokines in rheumatoid arthritis (RA) and spondyloartrhitits (SpA) including psoriatic arthritis. The IL-20 receptor (R) cytokines IL-19, IL-20, and IL-24 are produced in both the peripheral blood and the synovial joint and are induced by Toll-like receptor ligands and autoantibody-associated immune complexes in monocytes. IL-19 seems to have anti-inflammatory functions in arthritis. In contrast, IL-20 and IL-24 increase the production of proinflammatory molecules such as monocyte chemoattractant protein 1 and are associated with bone degradation and radiographic progression. IL-22 is also associated with progression of bone erosions. This suggests that the IL-22RA1 subunit shared by IL-20, IL-22, and IL-24 is important for bone homeostasis. In line with this, the IL-22RA1 has been found on preosteoclasts in early RA. IL-26 is produced in high amounts by myofibroblasts and IL-26 stimulation of monocytes is an important inducer of Th17 cells in RA. This indicates a role for IL-26 as an important factor in the interactions between resident synovial cells and infiltrating leukocytes. Clinical trials that investigate inhibitors of IL-20 (fletikumab) and IL-22 (fezakinumab) in psoriasis and RA have been terminated. Instead, it seems that the strategy for modulating the IL-20 cytokine family should take the overlap in cellular sources and effector mechanisms into account. The redundancy encourages inhibition of more than one cytokine or one of the shared receptors. All IL-20 family members utilize the Janus kinase signaling pathway and are therefore potentially inhibited by drugs targeting these enzymes. Effects and adverse effects in ongoing clinical trials with inhibitors of IL-22 and the IL-22RA1 subunit and recombinant IL-22 fusion proteins will possibly provide important information about the IL-20 subfamily of cytokines in the future.

• Keywords
• IL-10 family, autoantibody, cytokine, fibroblast, interleukin, osteoclast, rheumatoid arthritis, spondyloarthritis,
• MeSH
• Antibodies, Monoclonal, Humanized MeSH
• Interleukins antagonists & inhibitors   immunology   metabolism   MeSH
• Janus Kinases immunology   metabolism   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Antibodies, Monoclonal pharmacology   therapeutic use   MeSH
• Antibodies, Neutralizing pharmacology   therapeutic use   MeSH
• Osteoclasts immunology   metabolism   MeSH
• Arthritis, Psoriatic drug therapy   immunology   MeSH
• Receptors, Interleukin antagonists & inhibitors   immunology   metabolism   MeSH
• Arthritis, Rheumatoid drug therapy   immunology   MeSH
• Signal Transduction immunology   MeSH
• Broadly Neutralizing Antibodies MeSH
• Synovial Membrane cytology   immunology   metabolism   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• fezakinumab MeSH Browser
• Fletikumab MeSH Browser
• Antibodies, Monoclonal, Humanized MeSH
• IL19 protein, human MeSH Browser
• interleukin 20 MeSH Browser
• interleukin-22 receptor MeSH Browser
• interleukin-24 MeSH Browser
• Interleukins MeSH
• Janus Kinases MeSH
• Antibodies, Monoclonal MeSH
• Antibodies, Neutralizing MeSH
• Receptors, Interleukin MeSH
• Broadly Neutralizing Antibodies MeSH