Elevated levels of interleukin-18 and tumor necrosis factor-alpha in serum of patients with type 2 diabetes mellitus: relationship with diabetic nephropathy.

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. Copyright 2003 Elsevier Inc. All rights reserved.