Cytokine networks and cellular interactions in cartilage destruction in rheumatoid arthritis. This scheme represents the progressive destruction of the cartilage associated with the invading synovial pannus in rheumatoid arthritis. As a result of immune cell interactions involving T and B lymphocytes, monocyte/macrophages, and dendritic cells, several different cytokines are produced in the inflamed synovium as a result of the influx of inflammatory cells from the circulation and synovial cell hyperplasia. The upregulation of proinflammatory cytokines produced primarily in the synovium, but also by chondrocytes, results in the upregulation of cartilage-degrading enzymes, of the matrix metalloproteinase (MMP) and ADAM with thrombospondin-1 domains (ADAMTS) families, at the cartilage–pannus junction. Chemokines, nitric oxide (NO), and prostaglandins (PGs) also contribute to the inflammation and tissue catabolism. SDF, stromal cell-derived factor 1; TNF, tumor necrosis factor; TGF, transforming growth factor; IFN, interferon; Treg, regulatory T lymphocytes; Th, T helper cells.