Cytokines in the pathogenesis of rheumatoid arthritis

Cytokines regulate inflammation, autoimmunity and articular destruction in the joints of patients with rheumatoid arthritis. In particular, tumour-necrosis factor (TNF) has proved to be of particular utility as a therapeutic target.T-cell activation particularly towards a T helper 1 (TH1)-cell and/or a TH17-cell phenotype is associated with the presence in the synovial tissue of interleukin-15 (IL-15), IL-1, IL-6, transforming growth factor-β (TGFβ), IL-12 and IL-23. In turn, T cells drive inflammation via IL-17 release and by cognate interactions with adjacent macrophages.B cells have a critical role in synovitis, acting in part via antigen presentation and cytokine release. B-cell differentiation and expansion, in turn, is supported in the synovial tissue by IL-6, IL-10, B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL).Macrophage-derived cytokines including TNF, IL-1, IL-6, IL-15 and IL-18 drive many of the pro-inflammatory pathways in synovial tissue.Cytokines are responsible for osteoclast maturation and activation. There appears to be a hierarchical role for receptor activator of nuclear factor-κB ligand (RANKL) in this process together with TNF, IL-17 and IL-1.Early intervention, for example with TNF-blocking agents, appears to offer higher clinical response rates and improved chances of achieving clinical remission. Clinical studies are ongoing targeting IL-6, IL-15, IL-18, IL-17, granulocyte/macrophage colony-stimulating factor (GM-CSF) and others, with the objective of further improving clinical outcomes.