FK506 INHIBITS MURINE AA AMYLOIDOSIS WITHOUT MODULATING SERUM SAA LEVELS

摘要

AA amyloidosis can be induced during the clinical course of chronic inflammatory diseases including rheumatoid arthritis (RA), and chronic infections (1) AA amyloidosis is a systemic disorder and is characterized by extracellular deposition of amyloid containing serum amyloid A (SAA) and amyloid A protein (AA), proteolytically derived fragments of SAA, The serum concentration of this protein sometimes increases more than 1000-fold during inflammation, and exceeds 1 mg/ml SAA is mainly synthesized by hepatocytes, and its expression is stimulated by proinflammatory cytokines such as interleukin (IL)-1p IL-6, and tumor necrosis factor-ce (TNF-a) (2) It is well known that RA is the most frequent cause of AA amyloidosis Previous studies suggested that the primary objective of therapy for AA amyloidosis should be to lower the SAA levels (3), and thereby to reduce the supply of amyloid fibril precursor proteins. However, intriguing questions remain about the relationship between SAA concentrations and amyloid formation. Despite high to elevated serum SAA levels, most patients with chronic inflammatory disease do not develop AA amyloidosis.