Figure 1.

The role of macrophage migration inhibitory factor (MIF) in the pathogenesis of rheumatoid arthritis (RA). MIF stimulates the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-8, and prostaglandin from macrophages and synovial fibroblasts to induce matrix metalloproteinase (MMP)-1 and MMP-3, phospholipase A2, cyclooxygenase-2, which in RA patients may lead to tissue degradation. MIF also induces MMP-9 and MMP-13 in rat osteoblasts; a similar response may account for the bone destruction and osteoporosis characteristic of RA. MIF induces the production of vascular endothelial growth factor (VEGF) and IL-8 from synovial fibroblasts as well as endothelial tube formation. It also stimulates receptor activator of nuclear factor kB ligand (RANKL) production by RA synovial fibroblasts and causes differentiation of peripheral blood monocytes to mature osteoclasts. PGE2, prostaglandin E2; NO, nitric oxide; VCAM, vascular cell adhesion molecule; ICAM, intercellular adhesion molecule.