Advances in the treatment of rheumatoid arthritis (RA) are attributed to several aspects such as new classification criteria enabling early diagnosis and intensive treatment with the application of treat-to-target principles as well as better understanding of the pathogenesis of RA contributing to the development of targeted therapies. However, reaching remission is still not achieved in most patients with RA, which is one of the driving forces behind the continuous development of novel therapies and the optimization of therapeutic strategies. This review will outline several new therapeutic antibodies modulating anti-inflammatory cytokines interleukin (IL)-2 and IL-10 and pro-inflammatory mediators granulocyte-macrophage colony-stimulating factor, fractalkine, and IL-6 that are in various stages of clinical development as well as the progress in manufacturing biotechnologies contributing to the next generation of antibodies and their potential to expand the therapeutic armamentarium for RA. In addition, the fate of unsuccessful therapies including agents targeting IL-15, the IL-20 family, IL-21, chemokine CXCL10, B-cell activating factor (BAFF), and regulatory T (Treg) cells or a novel concept targeting synovial fibroblasts via cadherin-11 will be discussed.

• Klíčová slova
• biological therapies, monoclonal antibodies, rheumatoid arthritis, therapeutic strategies,
• MeSH
• cytokiny imunologie   MeSH
• fibroblasty účinky léků   MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• revmatoidní artritida terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• monoklonální protilátky MeSH

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.

• Klíčová slova
• IL-10 family, autoantibody, cytokine, fibroblast, interleukin, osteoclast, rheumatoid arthritis, spondyloarthritis,
• MeSH
• humanizované monoklonální protilátky MeSH
• interleukiny antagonisté a inhibitory   imunologie   metabolismus   MeSH
• Janus kinasy imunologie   metabolismus   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• monoklonální protilátky farmakologie   terapeutické užití   MeSH
• neutralizující protilátky farmakologie   terapeutické užití   MeSH
• osteoklasty imunologie   metabolismus   MeSH
• psoriatická artritida farmakoterapie   imunologie   MeSH
• receptory interleukinů antagonisté a inhibitory   imunologie   metabolismus   MeSH
• revmatoidní artritida farmakoterapie   imunologie   MeSH
• signální transdukce imunologie   MeSH
• široce neutralizující protilátky MeSH
• synoviální membrána cytologie   imunologie   metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fezakinumab MeSH Prohlížeč
• Fletikumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• IL19 protein, human MeSH Prohlížeč
• interleukin 20 MeSH Prohlížeč
• interleukin-22 receptor MeSH Prohlížeč
• interleukin-24 MeSH Prohlížeč
• interleukiny MeSH
• Janus kinasy MeSH
• monoklonální protilátky MeSH
• neutralizující protilátky MeSH
• receptory interleukinů MeSH
• široce neutralizující protilátky MeSH