Etanercept, a tumor necrosis factor-α antagonist usually used to treat inflammatory arthritis, decreased C-reactive protein levels and improved other inflammatory markers in patients with metabolic syndrome, reported Dr. L. Elizabeth Bernstein and her associates at Massachusetts General Hospital and Harvard Medical School, Boston.
Etanercept interferes with tumor necrosis factor-α's ability to bind with cell receptors, blocking the inflammatory response. The investigators examined the drug's effects on C-reactive protein (CRP) and other inflammatory markers associated with cardiovascular disease in 52 men and women with metabolic syndrome.
These subjects (mean age 46 years) had either hyperinsulinemia or impaired glucose tolerance; an elevated body mass index or a high waist-hip ratio; elevated serum triglycerides or low HDL cholesterol levels; and hypertension. All the subjects had elevated CRP levels at baseline, which was likely linked to an obesity-associated activation of the tumor necrosis factor system, since none had any other known inflammatory condition.
Half the subjects were randomly assigned to receive etanercept in two 25-mg subcutaneous injections weekly for 4 weeks, and the other half received placebo injections.
Etanercept reduced CRP levels by more than 2 mg/L, a 34% reduction within 4 weeks. Weight, nutritional status, and body composition remained unchanged, indicating that the drug acted independently of these factors to improve CRP, the researchers said (Arch. Intern. Med. 2006;166:902–8). At the same time, adiponectin levels rose significantly. Adiponectin, an adipocyte-derived cytokine that has anti-inflammatory and antiatherosclerotic properties, is decreased in obese people. Etanercept also decreased the subjects' markedly high levels of fibrinogen, a clotting factor and marker of inflammation and abnormal hemostasis. The drug also tended to reduce levels of interleukin-6 levels, another indicator of inflammation. It did not affect insulin sensitivity.
Etanercept was well tolerated in these subjects. However, they had been well screened before enrollment for contraindications to the drug, known to impair immune function in some patients. “Further studies with longer duration will be necessary to determine the safety” of etanercept in people with metabolic syndrome, the investigators noted.
The findings “suggest a novel and physiologically relevant approach to improve the increased inflammatory milieu associated with abdominal obesity” and metabolic syndrome. But additional studies are needed to investigate such a hypothesis.