Virus In Babies May Cause Asthma Later On

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Source: Washington University School Of Medicine

Date Posted: Thursday, July 11, 2002

Web Address: http://www.sciencedaily.com/releases/2002/07/020711075513.htm

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Virus In Babies May Cause Asthma Later On

St. Louis, July 15, 2002 —- 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

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 body's 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.

Holtzman's 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. "

Reference: 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 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 -Jewish and St. Louis

Children's hospitals. The School of Medicine is one of the leading medical

research, teaching and patient-care institutions in the nation. Through its

affiliations with -Jewish and St. Louis Children's hospitals, the

School of Medicine is linked to BJC HealthCare.

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