Marked Increases in Macrophage Colony-Stimulating Factor and Interleukin-18 in Maintenance Hemodialysis Patients: Comparative Study of Advanced Glycation End Products, Carboxymethyllysine and Pentosidine

Abstract

Background: Recent studies have demonstrated the crucial involvement of advanced glycation end products (AGEs) in major complications of long-term hemodialysis (HD) patients. HD, in a clinical setting, is characterized by increased production of proinflammatory cytokines. AGEs and cytokines are presumed to be responsible for the development of major complications in long-term HD. We therefore investigate here the relationship between a newly identified cytokine, interleukin-18 (IL-18), and two AGEs, carboxymethyllysine-hemoglobin (CML-Hb) and pentosidine. Methods: CML-Hb, pentosidine macrophage colony-stimulating factor (M-CSF), and IL-18 were evaluated in 35 patients undergoing stable maintenance HD. CML-Hb and pentosidine were measured by a dot blot and competitive ELISA. Cytokines were measured with a cytokine-specific ELISA. Results: Circulating levels of CML-Hb and pentosidine were elevated in HD patients as compared to controls. The serum values of M-CSF and IL-18 were significantly increased in the HD patients in comparison to controls. Moreover, these two AGEs and serum values of M-CSF, M-CSF and IL-18 showed significant correlation by simple and multiple regression analysis. Conclusion: Elevation of circulating IL-18 levels was demonstrated in maintenance HD patients relative to controls. A correlative increase in M-CSF and IL-18 suggests the presence of a primed state of monocytes/macrophages in HD patients.

Plasma Interleukin-18 Levels in Hemodialysis Patients: Increased by Dialysis Process and Association with Interleukin-6 and Tumor Necrotic Factor-α

“…Our observations are compatible with the fi ndings of Gangemi et al [15] and Uchimura et al [16] . Considering their reports and our fi ndings, several possible mechanisms might contribute to this high IL-18 level.…”

Plasma Interleukin-18 Levels in Chronic Renal Failure and Continuous Ambulatory Peritoneal Dialysis

“…All are characterized by chronic inflammation as is observed in patients with uremia [17,18]. Gangemi et al [7] and Uchimura et al [19] have shown that plasma levels of IL-18 are elevated in patients undergoing hemodialysis. In the current work, we demonstrate that plasma IL-18 concentrations are raised in patients with CRF and those undergoing CAPD (table 2).…”

Cytokine Dysregulation in Chronic Kidney Disease: How Can We Treat It?

“…Elevated plasma IL-18 levels are present in a number of inflammatory diseases, including rheumatoid arthritis, Crohn's disease, atherosclerosis [26] and CKD [27] . IL-18 levels have been shown to be increased in predialysis, HD and peritoneal dialysis (PD) patients [23,26,28,29] . As increased production of IFN-␥ is one of the main characteristics of the Th1 response, IL-18 accumulation in uremic patients may contribute to such a response also in HD patients [26,30] .…”