While most scientists believe that allergies cause asthma, researchers at Washington University School of Medicine in St. Louis are uncovering a second potential cause for this common respiratory illness. Their new model suggests that a viral infection in the first years of life may leave a lasting mark on the immune system, causing chronic respiratory problems later on.
"While the allergic response may increase during an asthma attack, our research suggests that the anti-viral response also increases," says Michael J. Holtzman, M.D., the Selma and Herman Seldin Professor of Medicine and professor of cell biology and physiology. "We think that a virus in infancy or childhood creates a hit-and-run effect, where a brief infection causes permanent changes in the bodys anti-viral system."
Holtzman led the study, which appears in the July 15 issue of the Journal of Clinical Investigation.
The most common cause of lower respiratory illness in children is paramyxoviral infection, which often results in chronic wheezing regardless of whether the child develops allergies. But researchers have yet to figure out how the short-term influence of this viral infection leads to a long-term condition of respiratory inflammation and distress.
Holtzmans team examined mice with bronchiolitis – inflamed airways – caused by paramyxoviral infection. The mouse disease mimics paramyxoviral infection in humans. These mice responded immediately to the infection – immune cells flooded the lining of the respiratory tract, attacking infectious cells and inflaming the tissues. Weeks after infection, the airways of the lung remained extremely sensitive, or hyperreactive, and the airway lining became populated with mucus-producing cells. Each of these changes – airway hyperreactivity and cellular remodeling – lasted for at least one year and perhaps indefinitely. "Since each of these changes also is a long-term symptom of asthma, these findings provide a link between the response to viral infection and the development of asthma," says Holtzman.
Uninfected mice that instead were exposed to a common experimental allergen, called ovalbumin, also developed similar inflammation of the airways, but these mice recovered by themselves within two and a half months.
To see what happens if the initial airway response was prevented, the researchers examined mice lacking the gene that encodes one of the main proteins that control immune-cell traffic, intercellular adhesion molecule-1 (ICAM-1). As expected, mice lacking ICAM-1 that were infected with this virus were initially healthier than their normal counterparts, with far less airway inflammation, less weight loss and lower mortality rates.
Interestingly, though, these genetically altered mice still developed chronic asthma-like changes similar to normal mice – they reached the same level of airway hyperreactivity and mucus-producing cells as normal mice by 11 weeks after infection.
The team also discovered that mice treated with glucocorticoid, a common anti-asthma medication, before cellular remodeling began were at least partially protected from the chronic effects of viral infection.
"Our findings raise the possibility that asthma not only resembles a persistent anti-viral response, but may actually be caused by one," says Holtzman. "These results in mice provide a further basis for determining exactly how similar events may develop in children and adults with asthma."
Walter MJ, Morton JD, Kajiwara N, Agapov E, Holtzman MJ. Viral induction of a chronic asthma phenotype and genetic segregation from the acute response. Journal of Clinical Investigation, Vol. 110, pg. 165 – 175, July 15, 2002.
Funding from the National Heart, Lung and Blood Institute, the American Lung Association, the Martin Schaeffer Fund and the Alan A. and Edith L. Wolff Charitable Trust supported this research.
The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.
Gila Reckess | EurekAlert
Scientists use nanoparticle-delivered gene therapy to inhibit blinding eye disease in rodents
08.07.2020 | Johns Hopkins Medicine
Deconstructing glioblastoma complexity reveals its pattern of development
08.07.2020 | McGill University
New insight into the spin behavior in an exotic state of matter puts us closer to next-generation spintronic devices
Aside from the deep understanding of the natural world that quantum physics theory offers, scientists worldwide are working tirelessly to bring forth a...
Kiel physics team observed extremely fast electronic changes in real time in a special material class
In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...
Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.
Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....
Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.
Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...
A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...
07.07.2020 | Event News
02.07.2020 | Event News
19.05.2020 | Event News
10.07.2020 | Life Sciences
10.07.2020 | Materials Sciences
10.07.2020 | Life Sciences