β₂-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 β₂-microglobulin (β₂M) 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 β₂M (AGE-β₂M) in the pathogenesis of HAA, we examined the effect of AGE-β₂M on macrophage production of interleukin-6 (IL-6), an important cytokine for osteoclastogenesis and bone resorption. Purified AGE-β₂M from long-term hemodialysis patients, but not normal β₂M, stimulated synthesis and secretion of IL-6 from macrophages. Similar effects were also induced by in vitro-prepared AGE-β₂M (normal β₂M incubated with glucose for 60 days in vitro). These findings suggested a potential role of AGE-β₂M in the pathogenesis of HAA.