Researchers from the University of Pennsylvania Medical Center and other institutions are starting to amass solid evidence to explain how a popular heart medication works on a molecular level. Specifically, the scientists investigated the role of cytokines (bodily proteins that regulate inflammation) in explaining the effectiveness of amlodipine, a widely prescribed calcium-channel blocker for patients with heart failure. "A better understanding of the relationship between cytokines and amlodipine will hopefully open the door to develop more effective therapies for congestive heart failure, a condition that affects about three million Americans," says Emile R. Mohler, III, MD, director of vascular medicine at Penn. Mohler presents his findings today at the European Congress of Cardiology in Stockholm Sweden.
Cytokines, an area of active research on many fronts, are proteins that regulate the intensity and duration of the inflammatory response. People suffering from heart failure, as well as many other diseases, have higher levels of two such proteins--tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)--circulating in their blood. "Inflammation is quite prevalent in heart disease, and amlodipine somehow dampens this inflammatory process," explains Mohler.
Researchers currently believe that the release of cytokines may affect the function of heart tissue by initiating programmed cell death in the myocardium. Over the course of 26 weeks, Mohler and his team found that amlodipine given to heart patients lowered their plasma levels of IL-6.
"I think the intriguing aspect of these results is that amlodipine may have a beneficial action in heart failure patients by reducing cytokines, although this has to be explored further in follow-up studies," says Mohler.
The research team postulated that cytokine levels may also have some prognostic value for treating heart disease. Using a statistical model, Mohler and his colleagues found that congestive heart failure or death was more likely to occur in patients with higher levels of IL-6. "By measuring cytokines it may help us to identify those patients who may respond better to therapy," he says. "For example, if cytokine levels tend to be lower, your chances of living longer with heart failure may be better."
Dr. Mohler's findings appear in the July 1997 issue of the Journal of the American College of Cardiology. This work was funded by the National Institutes of Health and Pfizer Corp.
Dr. Mohler can be reached at 215-662-9016 until Aug. 22, 1997, after which time he leaves for Sweden. He returns Aug. 29.
The University of Pennsylvania Medical Center's sponsored research ranks fifth in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation. In federal fiscal year 1996, the medical center received $149 million. In addition, for the second consecutive year, the institution posted the highest growth rate in research activity--9.1 percent--of the top-ten U.S. academic medical centers during the same period. News releases from the medical center are available to reporters by direct E-mail, fax, or U.S. mail, upon request. They are also posted to the center's home page (http://www.med.upenn.edu) and EurekAlert! (http://www.eurekalert.org), an Internet resource sponsored by the American Association for the Advancement of Science.