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.


CONCLUSIONS
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.
Uchimura
Tomonori
T
Department of Laboratory Medicine, Kagoshima University School of Medicine, Japan.
Motomiya
Yoshihiro
Y
Okamura
Haruki
H
Hashiguchi
Teruto
T
Miura
Masakazu
M
Uji
Yoshinori
Y
Iwamoto
Hisahiko
H
Maruyama
Ikuro
I
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood*; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D006435:Renal Dialysis
D016207:Cytokines; D017127:Glycation End Products, Advanced; D006454:Hemoglobins; D020382:Interleukin-18; C048496:N(6)-carboxymethyllysine; D016173:Macrophage Colony-Stimulating Factor; D001120:Arginine; C062187:pentosidine; D008239:Lysine