BETA(2)-MICROGLOBULIN MODIFIED WITH ADVANCED GLYCATION END-PRODUCTS INDUCES INTERLEUKIN-6 FROM HUMAN MACROPHAGES - ROLE IN THE PATHOGENESIS OF HEMODIALYSIS-ASSOCIATED AMYLOIDOSIS

Recently, we demonstrated that beta(2)-microglobulin (beta(2)M) of amyloid deposits in hemodialysis-associated amyloidosis (HAA), a serious complication leading to hemodialysis arthropathy, is modified with advanced glycation end products (AGEs) of the Maillard reaction. In the present study, to elucidate the possible involvement of AGEs-modified beta(2)M (AGE-beta(2)M) in the pathogenesis of HAA, we examined the effect of AGE-beta(2)M on macrophage production of interleukin-6 (IL-6), an important cytokine for osteoclastogenesis and bone resorption. Purified AGE-beta(2)M from long-term hemodialysis patients, but not normal beta(2)M, stimulated synthesis and secretion of IL-6 from macrophages. Similar effects were also induced by in vitro-prepared AGE-beta(2)M (normal beta(2)M incubated with glucose for 60 days in vitro). These findings suggested a potential role of AGE-beta(2)M in the pathogenesis of HAA. (C) 1994 Academic Press, Inc.