Enhancement by iron of interleukin 1 induced granulocyte macrophage colony stimulating factor (GM-CSF) production by human synovial fibroblasts

Iron infusion activates synovium and induced joint inflammation in experimental animals and causes the flaring up of arthritis in patients with rheumatoid arthritis (RA). Marked iron deposition in RA synovia has been reported over the past 30 years and has also recently been demonstrated by quantitative photometric assessment and is correlated with exudative and proliferative histological features.1 It has been reported that the amount of iron deposition in RA synovial tissue is correlated with disease activity and severity. Iron has an important role in RA synovitis through the formation of radical oxygen species, and the enhancement of collagen synthesis and synovial fibroblast proliferation2 possibly owing to down regulation of prostaglandin E2 (PGE2) production.3 Synovial fibroblasts produce a number of inflammatory mediators including cytokines such as interleukin (IL)1, IL6, IL8, fibroblast growth factor, vascular endothelial growth factor, tumour necrosis factor, and granulocyte macrophage colony stimulating factor (GM-CSF). GM-CSF produces the progenitor cells of macrophage lineage stem cells and stimulates mature granulocytes and macrophages. GM-CSF is produced by T cells, macrophages, and fibroblasts and has been found in synovial fluid and tissue from patients with RA. GM-CSF has an important role in type II collagen induced arthritis in rats and in the acute methylated bovine …