Adrenomedullin in synovial fluids from patients with rheumatoid arthritis inhibits interleukin 6 production from synoviocytes

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Abstract
A drenomedullin (AM) is a hypotensive peptide found in human pheochromocytoma tissue, which comprises 52 amino acids with an intramolecular disulphide bond.1,2 The ring structure and amidated C-terminus of AM are critical for its receptor binding and hypotensive activity. The mature AM is synthesised as glycine extended AM followed by C-terminal amidation to assume a biologically active form in tissues. AM has a vasorelaxant effect, antagonising the vasospastic effect of endothelin-1 (ET-1). Recently, proinflammatory cytokines, such as tumour necrosis factors α (TNFα) and interleukin-1 (IL1), were found to stimulate production and secretion of AM from vascular endothelial cells and vascular smooth muscle cells in vitro, suggesting that AM interacts with the immune system.3 However, AM reduces the production of TNFα from macrophages stimulated with lipopolysaccharide. In addition, AM shows an anti-inflammatory effect that reduces the production of …