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Vol. 46. Issue 9.
Pages 459-465 (July 2010)
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Vol. 46. Issue 9.
Pages 459-465 (July 2010)
Original Article
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Time Trends of Th1 and Th2 Cytokines in Induced Sputum of Asthmatic Subjects During Acute Upper Respiratory Viral Infections
Tendencias temporales de las concentraciones de citocinas Th1 y Th2 en esputo inducido de pacientes asmáticos durante infecciones víricas agudas de las vías respiratorias superiores
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Ding Zhang, Jingwen Xia, Xiaodong Chen
Corresponding author
xdchen8@hotmail.com

Corresponding author.
Department of Respiratory Disease, Huashan Hospital, Fudan University, Shanghai, China
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Abstract
Fundamentals

Many asthma exacerbations are caused by respiratory viral infections that induce the interplay between Th1 and Th2 immune responses. However, the time trends for Th1 and Th2 immune responses during these phenomena have not been well studied.

Objective

To identify possible mechanisms underlying the link between respiratory viral infections and asthma exacerbations.

Patients and methods

We recruited 40 adults aged 21-58 years for 4 groups. A. Healthy, B. Healthy with viral infection, C. Mild to moderate asthma and D. Same as C, but with viral infection. Th1 and Th2 cytokines in induced sputum samples during the course of acute upper respiratory viral infections in otherwise healthy and asthmatic individuals were monitored. IL-4, IL-5 and IFN-γ were assayed by ELISA. Viral infection symptoms and asthma severity scores were monitored. Time trends were analyzed using linear mixed models.

Results

IL-4 and IL-5 levels in groups C and D were higher than in groups A and B. IFN-γ levels and viral infection symptoms scores in group B spiked by day 2 and rapidly declined by day 7, while in group D, IFN-γ and symptoms scores for viral infection and asthma peaked much later (days 3-5) and slowly declined. The ratios of IL-4 and IL-5 to IFN-γ in group D were significantly higher than in group C.

Conclusions

Infection-induced asthma exacerbations may be due to impaired anti-viral Th1-immune responses. There appears to be a critical window of 3-5 days for therapeutic intervention.

Keywords:
Upper airway viral infection
Asthma exacerbation
Interleukin 4
Interleukin 5
Interferon-γ
Th1/Th2 balance
Induced sputum
Resumen
Fundamento

Muchas de las exacerbaciones del asma se deben a infecciones víricas de las vías respiratorias que inducen una interacción de respuestas inmunitarias entre Th1 y Th2. Sin embargo, las tendencias temporales de estas respuestas durante estos fenómenos no se han estudiado con detalle.

Objetivo

Identificar los posibles mecanismos subyacentes de la relación entre las infecciones víricas respiratorias y las exacerbaciones del asma.

Pacientes y métodos

Seleccionamos 40 adultos, de 21-58 años de edad, en 4 grupos: A, sanos; B, sanos con infección vírica; C, con asma leve o moderada, y D, igual que C pero con infección vírica. Durante el curso de una infección vírica aguda de las vías respiratorias superiores se monitorizaron las citocinas Th1 y Th2 en muestras de esputo inducido en individuos por lo demás sanos y en pacientes asmáticos. La interleucina (IL) 4, la IL-5 y el interferón gamma (IFN-γ) se analizaron mediante un método ELISA. Se monitorizaron las puntuaciones de los síntomas de infección vírica y de gravedad del asma. Las tendencias temporales se analizaron mediante la utilización de modelos mixtos lineales.

Resultados

En los grupos C y D los valores de IL-4 e IL-5 fueron mayores que en los grupos A y B. En el grupo B, los valores de IFN-γ y las puntuaciones de síntomas de infección vírica fueron máximos en el día 2 y disminuyeron rápidamente en el día 7, mientras que en el grupo D los valores de IFN-γ y las puntuaciones de síntomas de infección vírica y de asma alcanzaron un máximo mucho más tarde (días 3-5) y disminuyeron lentamente. En el grupo D, los cocientes IL-4 e IL-5:IFN-γ fueron significativamente más altos que en el grupo C.

Conclusiones

Las exacerbaciones del asma inducidas por las infecciones pueden deberse a un deterioro de las respuestas inmunitarias antivíricas Th1. Parece identificarse un intervalo decisivo de 3-5 días para instaurar una intervención terapéutica.

Palabras clave:
Infección vírica de las vías respiratorias
superiores
Exacerbación del asma
Interleucina 4
Interleucina 5
Interferón-γ
Equilibrio Th1/Th2
Esputo inducido
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Both authors have contributed equally to the investigation.

Copyright © 2010. Sociedad Española de Neumología y Cirugía Torácica
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