Advanced glycation end products stimulate tumor necrosis factor-alpha and interleukin-1 beta secretion by peritoneal macrophages in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND Advanced glycation end products, formed by the non-enzymatic glycation of proteins with reducing sugars, are thought to play a pathogenetic role in the vascular complications of diabetes, uremia and atherosclerosis. 132-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis. AGE1-modified beta2m has been found in amyloid deposits of long-term hemodialysis patients. AGE-modified 132m has also been shown to enhance chemotaxis and increase tumor necrosis factor-alpha and interleukin-1 beta secretion by circulating and tissue monocytes/macrophages. OBJECTIVES To investigate the effect of AGE-modified 132m and AGE-human serum albumin on TNF-alpha and IL-1beta secretion by human peritoneal macrophages derived from patients on continuous ambulatory peritoneal dialysis. METHODS Human PMO were isolated from peritoneal dialysis effluent of stable CAPD patients and were incubated for 24 hours with AGE-modified beta2m, beta2m, AGE-HSA, HSA or lipopolysaccharide. TNF-alpha or IL-1beta secretion was measured by enzyme-linked immunosorbent assay in cell-free culture supernatants. RESULTS Both AGE-modified beta2m and AGE-HSA significantly increased TNF-alpha and IL-1beta secretion by human PMO in a dose-dependent manner (50-200 microg/ml). In contrast, beta2m or HSA had no such stimulatory effect on TNF-alpha secretion but had a small significant increase in IL-1beta secretion. CONCLUSIONS AGE-modified beta2m promotes in vitro TNF-alpha and IL-13 secretion by human PMO of CAPD patients. Activation of these macrophages by AGE-modified beta2m may be a contributory factor to the morphologic changes and altered permeability of the peritoneal membrane in long-term CAPD.