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 [plusmn] 11.9 pg/mL v 172.8 [plusmn] 7.7 pg/mL, P [lt ] .0001; TNF-[alpha ], 2.41 [plusmn] 0.18 pg/mL v 0.46 [plusmn] 0.18 pg/mL, P [lt ] .0001), whereas that of IL-6 was not different between the two groups (0.73 [plusmn] 0.10 pg/mL v 0.65 [plusmn] 0.08 pg/mL, difference not significant [lsqb ]NS[rsqb ]), 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 ([lt ]30 [mu ]g/mg creatinine, 252.7 [plusmn] 16.4 pg/mL; 30 to 300 [mu ]g/mg creatinine, 352.7 [plusmn] 35.2 pg/mL; [gt ]300 [mu ]g/mg creatinine, 350.0 [plusmn] 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 [plusmn] 0.41 pg/mL v 1.94 [plusmn] 0.18 pg/mL; IL-6, 1.64 [plusmn] 1.11 pg/mL v 0.51 [plusmn] 0.05 pg/mL, P [lt ] .05, respectively). These results suggest that serum levels of IL-18, TNF-[alpha ], and IL-6 may have some etiopathogenic roles in diabetic nephropathy. [copy ] 2003 Elsevier Inc. All rights reserved.