April 28, 2006

Blocking key protein reduces inflammatory markers in metabolic syndrome

MGH researchers have shown that blocking the action of a critical protein can improve multiple inflammatory pathways in patients with metabolic syndrome — a cluster of symptoms associated with increased risk of cardiovascular disease and type 2 diabetes. "This proof of principle sheds light on the physiology of inflammation and its relation to cardiac risk in obese patients," says Steven Grinspoon, MD, of the MGH Program in Nutritional Metabolism and Neuroendocrine Unit and the report's senior author.

Metabolic syndrome is a group of symptoms that includes abdominal obesity, high triglycerides and LDL ("bad") cholesterol along with low HDL ("good") cholesterol, insulin resistance and abnormal levels of several inflammatory proteins.

Estimated to affect more than 50 million Americans currently, metabolic syndrome increases the risk of heart attack, stroke and other cardiovascular disorders, as well as type 2 diabetes. While there are many questions about the mechanism behind metabolic syndrome, current evidence suggests that inflammatory proteins released by abdominal fat may be an underlying cause.

The current study, published in the April 24 issue of Archives of Internal Medicine, examined whether the drug etanercept (Enbrel) might reduce the inflammatory effects of metabolic syndrome. Etanercept blocks the action of tumor necrosis factor (TNF), an inflammatory protein released by fat cells and known to increase insulin resistance.

The researchers enrolled 56 patients who met standard criteria for metabolic syndrome. Half of them received weekly injections of etanercept and half received a placebo during the four-week study period. At the end of the study the levels of several key inflammatory markers were significantly lower in participants who received etanercept, and levels of a factor that reflects reduced inflammation had increased, also suggesting lower cardiovascular risk.

"It has been speculated that blocking TNF could reduce systemic inflammation in abdominally obese people, and we are very excited that giving this drug had such a dramatic effect on these major markers," Grinspoon says. The study's co-authors are first author Elizabeth Bernstein, MD, Jacqueline Berry, Sunnie Kim and Bridget Canavan — all of the MGH.