Research suggests beta agonists may alter the immune system
WINSTON-SALEM, N.C. – New research at Wake Forest University School of Medicine suggests that certain inhaled asthma medications – as well as similar chemicals our bodies produce during times of high stress – may worsen diseases such as asthma, heart failure and lupus that involve inflammation.
The scientific team led by Raymond Penn, Ph.D., and Matthew Loza, Ph.D, found that beta-agonists, such as those used in the treatment of asthma, increase the accumulation of type 2 T cells, a type of white blood cell that participates in immune system defense mechanisms. In certain diseases such as asthma and lupus, an over-reactive type 2 T cell response occurs and is believed to contribute to the disease.
"Inhaled beta-agonists are very effective in opening up airways and allowing asthmatics to breathe, but their ability to address the underlying inflammation that causes most asthma has been debated for years," said Penn, an associate professor in the Department of Internal Medicine and the Center for Human Genomics.
The research is reported on-line in the Journal of Allergy and Clinical Immunology and will be published in an upcoming print issue.
In fact, numerous clinical studies have reported that asthma symptoms tend to worsen over time in patients on continuous beta-agonist therapy. Although the reasons for this deterioration of asthma control are not clear, the Food and Drug Administration now recommends that the treatment of asthma with long-acting beta-agonists be supplemented with inhaled anti-inflammatory medications.
Using blood samples from human participants, the scientists measured the effect of beta-agonists on white blood cells that were grown in the laboratory. They were surprised to find that the drugs promoted a preferential accumulation of type 2 T cells.
Beta-agonists belong to a class of chemicals that include the hormone adrenaline produced by the body. Consequently, conditions that elevate blood adrenaline, such as emotional stress or heart failure, may also have the ability to alter the immune system by increasing type 2 T cells, and thereby promote or worsen disease.
"Although further research is needed to confirm that these findings occur in the human body, our research points to an important means by which the immune system is regulated by both therapies and the hormonal system," Penn said. "From an asthma management standpoint, these studies further emphasize the need to include anti-inflammatory corticosteroids when treating moderate to severe asthma."
The researchers also uncovered the mechanism which by beta-agonists increased type 2 T cells. They found that the beta-agonists were unable to effectively stimulate the enzyme protein kinase A (PKA). Other molecules similar to beta-agonists that were able to strongly activate PKA also inhibited the ability of type 2 T cells to proliferate and survive. Penn said this finding could influence future drug development, because new beta agonists that are more effective in activating PKA may prove useful.
The research was funded by grants provided by the Heart, Lung, and Blood Institute of the National Institute of Health. Co-researchers were Stephen P. Peters, M.D., Ph.D., Susan Foster, Ph.D., and Islam U. Khan, Ph.D., all with Wake Forest.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. The system comprises 1,187 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.
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