Asthma is a common inflammatory disorder with two types: the more severe is genetic, and accounts for about 30 percent of cases; the less severe is allergic, or caused by the environment, accounting for 70 percent of cases. Although doctors have long thought that the damage asthma causes is limited to the lungs, UCLA researchers now believe it may also be harmful to other organs. In a study funded by the National Institute for Allergy and Infectious Disease and published in the Nov. 2014 issue of Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, researchers found that genetic damage is present in circulating blood, which could cause effects to the body beyond the lungs.
IL-13 and inflammation
In the study, titled "IL-13 Overexpression in Mouse Lungs Triggers Systemic Genotoxicity in Peripheral Blood," researchers studied the effects of the overexpression of a cytokine called interleukin 13 (IL-13) during asthma attacks. The release of this cytokine stimulates inflammation, causing genetic damage and permanent changes to the lungs.
According to senior author Robert Schiestl, PhD, a professor of pathology and radiation oncology at the David Geffen School of Medicine at UCLA, the study was the first to assess the role of IL-13 in genotoxicity, or genetic damage to cells. The researchers used genetically modified mice to simulate human asthma for study.
Genotoxicity and oxidative stress
Dr. Schiestl explained that "It appears that IL-13 increases important elements of the inflammatory response, including the creation of reactive oxygen species molecules," or ROS. These tiny molecules include free radicals that can damage cell DNA proteins, carbohydrates and lipids, resulting in a degenerative condition called oxidative stress. His research team found that this oxidative stress caused genetic damage in the circulating blood, resulting in oxidative DNA damage, single and double DNA strand breaks, micronucleus formation and protein damage. According to Schiestl, all of these effects can cause chromosomes to become unstable, possibly leading to diseases in other organs of the body.
Although asthma affects more than 25 million Americans, including about 7 million children, it cannot yet be cured — only managed. A better understanding of this disease is necessary for researchers and physicians to develop improvements in treatment and better serve asthmatic patients. Because asthma is such a complex disease, research findings on its development, mechanisms and effects are key for creating a complete scientific picture that could one day lead to a cure.