Two newly published studies in the September 17, 2004 issue of Science give rise to the possibility of developing drug therapies that target eosinophils, white blood cells long known to be associated with the asthma. The studies discount a 2000 study published in The Lancet which concluded that eosinophils do not have a significant role in the development of asthma in humans.
"The new studies clearly show evidence that eosinophils have a role in asthma. The question is how significant is that role? If these cells turn out to be important, they will be good drug targets," said Marsha Wills-Karp, PhD, chair of the division of immunobiology at Cincinnati Children's Hospital Medical Center. Dr. Wills-Karp is first author of a commentary that accompanies the studies. The second author is Christopher L. Karp, MD, director of molecular immunology at Cincinnati Children's.
The two individual studies were conducted by James J. Lee, PhD, of the Mayo Clinic, and Alison A. Humbles, PhD, of Children's Hospital Boston.
The results of both studies are based on experiments using mice without eosinophils. The researchers use different approaches to measure whether the absence of eosinophil cells can lead to asthma.
The studies address an age-old question in asthma research: Do white blood cells called eosinophils play a role in causing asthma? Eosinophils have long since been identified in the lungs of people with asthma, but it wasn't clear whether eosinophils actually contributed to asthma.
In the first study, Lee suggests that eosinophils are essential for asthma to develop. On the other hand, the Humbles study suggests that they are only important in one aspect of the disease: in the long-term effects of asthma on lung structure, rather than being instrumental in triggering the initial attack.
Experts have suggested that eosinophils have a key role in the development of asthma in children. But The Lancet study called into question theories that eosinophils were significant in the development of asthma. The new studies in Science show that eosinophils do indeed have a key role in the development of asthma, but how and to what extent isn't clear.
"Eosinophils had been one of the major targets of drug companies for years. But The Lancet study, which was the first such study in humans, surprised everyone when it showed those cells were not important in the immediate symptoms of asthma. It was very confusing and disheartening to many people when this study in humans did not support this line of development," Dr. Wills-Karp said.
The current studies use two different tools, both of which are considered to offer fairly definitive results. So, why then are there different results? One reason may be that eosinophils play an important role in asthma in some individuals, but not others depending on their genetic background. This is particularly relevant to human disease since asthma is clearly a heterogeneous disease that occurs through the interaction of many genes. Thus the differences observed between the two current studies may reflect the heterogeneity within the human population, Dr. Wills-Karp said.
"As there are likely many underlying causes of asthma, there may not be any one magic bullet for the treatment of asthma. The wave of the future for asthma may be a pharmacogenetic approach in which you tailor drug therapies to individuals based on genetic factors. This approach is being taken in many areas of medicine," Dr. Wills-Karp said.
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© 2004, Cincinnati Children's Hospital Medical Center
Lee JJ, Dimina D, Macias MP, Ochkur SI, McGarry MP, O'Neill KR, Protheroe C, Pero R, Nguyen T, Cormier SA, Lenkiewicz E, Colbert D, Rinaldi L, Ackerman SJ, Irvin CG, Lee NA.
Defining a link with asthma in mice congenitally deficient in eosinophils.
Science. 2004 Sep 17;305(5691):1773-6.
Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xanthou G, McKenna EE, Ghiran S, Gerard NP, Yu C, Orkin SH, Gerard C.
A critical role for eosinophils in allergic airways remodeling.
Science. 2004 Sep 17;305(5691):1776-9.
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