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
NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases
Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.
Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...
16.03.2018 | Event News
13.03.2018 | Event News
08.03.2018 | Event News
16.03.2018 | Earth Sciences
16.03.2018 | Physics and Astronomy
16.03.2018 | Life Sciences