Adipose-derived cytokines, including tumor necrosis factor α, may contribute to the inflammation in metabolic syndrome. Bernstein et al conducted a randomized, double-blind, placebo-controlled trial to investigate the effects of inhibition of tumor necrosis factor α with etanercept treatment in patients with the metabolic syndrome. C-reactive protein level decreased significantly in the etanercept group compared with the placebo group. Fibrinogen level decreased, interleukin 6 level tended to decrease, and adiponectin level increased in the etanercept-treated subjects compared with the placebo group. There were no changes in body composition parameters or insulin sensitivity, but high-density lipoprotein level tended to decrease in the etanercept group compared with the placebo group. The data demonstrate that etanercept reduces the C-reactive protein level and tends to improve other inflammatory cardiovascular risk indexes in patients with the metabolic syndrome, suggesting that etanercept may interrupt the inflammatory cascade that occurs in this context.