Scheme of the activation cascade from T lymphocytes (TL) to monocyte-macrophages (Mφ) and fibroblasts/synoviocytes (F/S). Activated TL trigger Mφ to produce proinflammatory cytokines that in turn induce the production of matrix-destructive metalloproteinases (MMPs) and prostaglandin E2 (PGE2), the latter products being involved in cartilage destruction and bone resorption. These processes are controlled by proinflammatory factors (IL-15, IL-2, IL-18, IL-17) and anti-inflammatory factors (IL-4, IL-10, granulocyte/macrophage colony stimulating factor [GM-CSF], IFN-β). Furthermore, naturally occurring inhibitors (IL-1sRII, IL-1Ra, tumor necrosis factor [TNF]sRI, TNFsRII) inhibit the activity of IL-1 and TNF-α, the production of which is blocked by apolipoprotein (apo) A-I and decreased by exogenous antibodies to CD69 and β2-integrins (CD11b>CD11c>CD11a). APC, antigen presenting cells; DC, dendritic cells.