Research suggests drugs may worsen inflammatory disease

The scientific team 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 some inflamatory diseases 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 Raymond Penn, an associate professor in the Department of Internal Medicine and the Center for Human Genomics.

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 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.

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). The researchers said this finding could influence future drug development, because new beta agonists that are more effective in activating PKA may prove useful.