title: Elevated levels of interleukin-18 and tumor necrosis factor-alpha in serum of patients with type 2 diabetes mellitus: relationship with diabetic nephropathy.
abstract: To compare levels of interleukin (IL)-18, tumor necrosis factor-alpha (TNF-alpha), and IL-6 in serum, we studied 151 type 2 diabetes mellitus patients with various degrees of nephropathy, as well as 80 healthy volunteers. IL-18, TNF-alpha, and IL-6 in serum were measured using an enzyme-linked immunosorbent assay (ELISA) with the respective mouse monoclonal antibodies. Significant differences in serum levels of IL-18 and TNF-alpha were observed between the patients and control subjects (IL-18, 278.0 +/- 11.9 pg/mL v 172.8 +/- 7.7 pg/mL, P <.0001; TNF-alpha, 2.41 +/- 0.18 pg/mL v 0.46 +/- 0.18 pg/mL, P <.0001), whereas that of IL-6 was not different between the two groups (0.73 +/- 0.10 pg/mL v 0.65 +/- 0.08 pg/mL, difference not significant [NS]), although patients with nephropathy showed higher levels. In addition, IL-18 levels were increased in diabetic patients with the development of urinary albumin excretion, with the highest found in those with microalbuminuria (<30 micro g/mg creatinine, 252.7 +/- 16.4 pg/mL; 30 to >300 micro g/mg creatinine, 352.7 +/- 35.2 pg/mL; >>300 micro g/mg creatinine, 350.0 +/- 16.0 pg/mL). Similarly, TNF-alpha and IL-6 in diabetic patients with microalbuminuria or clinical albuminuria were significantly increased as compared with those without albuminuria (TNF-alpha, 3.20 +/- 0.41 pg/mL v 1.94 +/- 0.18 pg/mL; IL-6, 1.64 +/- 1.11 pg/mL v 0.51 +/- 0.05 pg/mL, P <.05, respectively). These results suggest that serum levels of IL-18, TNF-alpha, and IL-6 may have some etiopathogenic roles in diabetic nephropathy.
authors.affiliation: Department of Internal Medicine and the Laboratory of Host Defenses Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Moriwaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Shibutani
authors.forename: Eiji
authors.initials: E
authors.lastname: Aoki
authors.forename: Zenta
authors.initials: Z
authors.lastname: Tsutsumi
authors.forename: Sumio
authors.initials: S
authors.lastname: Takahashi
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Koga
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuchi
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hada
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000097:blood* / Q000473:pathology* / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D020382:Interleukin-18; D015850:Interleukin-6; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha