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L. Elizabeth Bernstein, MD; Jacqueline Berry, BA; Sunnie Kim, BA; Bridget Canavan, BA; Steven K. Grinspoon, MD

Arch Intern Med. 2006;166:902-908.

Background  Adipose-derived cytokines, including tumor necrosis factor , may contribute to the inflammation that occurs in the metabolic syndrome. We investigated the effects of inhibition of tumor necrosis factor with etanercept in patients with the metabolic syndrome.

Methods  Fifty-six subjects with the metabolic syndrome were randomized to administration of either etanercept or identical placebo, 50 mg subcutaneously once a week for 4 weeks. The C-reactive protein level was the primary end point. Effects on other inflammatory markers (including fibrinogen, interleukin 6, and adiponectin), insulin sensitivity, lipid levels, and body composition were also determined.

Results  Baseline characteristics were similar between the groups. Two subjects dropped out of each group, and etanercept was well tolerated throughout the study. The C-reactive protein levels decreased significantly in the treated compared with the placebo group (–2.4 ± 0.4 vs 0.5 ± 0.7 mg/L; P<.001). Adiponectin levels rose significantly in the etanercept group compared with the placebo group (0.8 ± 0.4 vs –0.3 ± 0.3 µg/mL; P = .03). Fibrinogen levels decreased (–68 ± 16 vs –2 ± 31 mg/dL [–2.0 ± 0.47 vs –0.06 ± 0.91 µmol/L]; P = .04) and interleukin 6 levels tended to decrease (–1.2 ± 0.8 vs 0.5 ± 0.5 ng/L; P = .07) in the etanercept-treated subjects compared with placebo, respectively. No changes occurred in body composition parameters or insulin sensitivity, but high-density lipoprotein levels tended to decrease in the etanercept group (–1 ± 1 vs 2 ± 1 mg/dL [–0.03 ± 0.03 vs 0.05 ± 0.03 mmol/L]; P = .06) compared with the placebo group.

Conclusions  Etanercept reduces C-reactive protein levels and tends to improve other inflammatory cardiovascular risk indexes in patients with the metabolic syndrome. Etanercept may interrupt the inflammatory cascade that occurs with abdominal obesity. Further, longer-term studies are needed to determine the effects of tumor necrosis factor inhibition on cardiovascular disease in patients with the metabolic syndrome.

Author Affiliations: Program in Nutritional Metabolism and the Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston.

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