Marked increases in macrophage colony-stimulating factor and interleukin-18 in maintenance hemodialysis patients: comparative study of advanced glycation end products, carboxymethyllysine and pentosidine.

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.