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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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Article information
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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References
[1.]
M. Masoli, D. Fabian, S. Holt, R. Beasley.
The global burden of asthma: Executive summary of the GINA Dissemination Committee report.
[2.]
S.L. Johnston, P.K. Pattemore, G. Sanderson, S. Smith, F. Lampe, L. Josephs, et al.
Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.
BMJ, 310 (1995), pp. 1225-1229
[3.]
K.G. Nicholson, J. Kent, D.C. Ireland.
Respiratory viruses and exacerbations of asthma in adults.
BMJ, 307 (1993), pp. 982-986
[4.]
Y.Z. Zhang, X.D. Chen, J. Zhang, Z. Chen.
Clinical analysis of respiratory tract viral infection-induced asthma attacks.
J Clin Pulm Med, 10 (2005), pp. 746-747
[5.]
L.C. Borish, H.S. Nelson, J. Corren, G. Bensch, W.W. Busse, J.B. Whitmore, et al.
Efficacy of soluble IL-4 receptor for the treatment of adults with asthma.
J Allergy Clin Immunol, 107 (2001), pp. 963-970
[6.]
T. Yamagata, M. Ichinose.
Agents against cytokine synthesis or receptors.
Eur J Pharm, 533 (2006), pp. 289-301
[7.]
M.J. Leckie, A. Brinke, J. Khan, Z. Diamant, B.J. O’Connor, C.M. Walls, et al.
Effects of an interleukin-5 blocking monoclonal antibody on eosinophils airway hyperresponsiveness and the late asthmatic response.
Lancet, 356 (2000), pp. 2144-2148
[8.]
S.A. Bryan, B.J. O’Connor, S. Matti, M.J. Leckie, V. Kanabar, J. Khan, et al.
Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response.
Lancet, 356 (2000), pp. 2149-2153
[9.]
O. Holz, M. Mücke, P. Zarza, D. Loppow, R.A. Jÿrres, H. Magnussen.
Freezing of homogenized sputum samples for intermittent storage.
Clin Exp Allergy, 31 (2001), pp. 1328-1331
[10.]
E. Jaksztat, O. Holz, K. Paasch, M.M. Kelly, F.E. Hargreave, G. Cox, et al.
Effect of freezing of sputum samples on flow cytometric analysis of lymphocyte subsets.
Eur Respir J, 24 (2004), pp. 309-312
[11.]
J. Beier, K.M. Beeh, O. Kornmann, R. Buhl.
Stability of glutathione in induced sputum: Impact of freezing.
Respiration, 70 (2003), pp. 523-527
[12.]
P. Prince, M. Bertrand, M.E. Boulay, M.C. Bernier, L.P. Boulet.
Optimization of the conditions for preservation of induced sputum: Influence of freezing on cellular analysis.
Chest, 128 (2005), pp. 980-985
[13.]
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2006 [accessed 2009 Mar 23]. Available from: http://www.ginasthma.com.
[14.]
T.A. Popov, M.M. Pizzichini, E. Pizzichini, R. Kolendowicz, Z. Punthakee, J. Dolovich, et al.
Some technical factors influencing the induction of sputum for cell analysis.
Eur Resp J, 8 (1995), pp. 559-565
[15.]
T.A. Popov, R. Gottschalk, R. Kolendowicz, J. Dolovich, P. Powers, F.E. Hargreave.
The evaluation of a cell dispersion method of sputum examination.
Clin Exp Allergy, 24 (1994), pp. 778-783
[16.]
D.E. Parry, W.W. Busse, K.A. Sukow, C.R. Dick, C.A. Swenson, J.E. Gern.
Rhinovirus-induced peripheral blood mononuclear cell responses and outcome of experimental infection in allergic subjects.
J Allergy Clin Immunol, 105 (2000), pp. 692-698
[17.]
J.E. Gern, R. Vrtis, K.A. Grindle, C. Swenson, W.W. Busse.
Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection.
Am J Respir Crit Care Med, 162 (2000), pp. 2226-2231
[18.]
A.B. Kay, S. Ying, V. Varney, M. Gaga, S.R. Durham, R. Moqbel, et al.
Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4,IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced latephase cutaneous reactions in atopic subjects.
J Exp Med, 173 (1991), pp. 775-778
[19.]
D.S. Robinson, Q. Hamid, S. Ying, A. Tsicopoulos, J. Barkans, A.M. Bentley, et al.
Predominant TH-2 like bronchoalveolar T-lymphocyte populations in atopic asthma.
N Engl J Med, 326 (1992), pp. 298-304
[20.]
S. Till, S. Durham, R. Dickason, D. Huston, J. Bungre, S. Walker, et al.
IL-13 production by allergen-stimulated T cells is increased in allergic disease and associated with IL-5 but not IFN-gamma expression.
Immunology, 91 (1997), pp. 53-57
[21.]
E. Truyen, L. Coteur, E. Dilissen, L. Overbergh, J.L. Ceuppens, D. Bullens.
Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients.
Thorax, 61 (2006), pp. 202-208
[22.]
A. Hamzaoui, M.B. Brahim, A. Zhioua, K. Ayed, K. Hamzaoui.
Inflammatory response in induced sputum mononuclear cells from patients with acute exacerbation of asthma.
Mediators Inflamm, 9 (2000), pp. 147-153
[23.]
S. Romagnani.
Regulatory T cells: Which role pathogenesis and treatment of allergic disorders?.
[24.]
O. Akbari, J.L. Faul, E.G. Hoyte, G.J. Berry, J. Wahlström, M. Kronenberg, et al.
CD4t invariant T-cell-receptor natural killer T cells in bronchial asthma.
N Engl J Med, 354 (2006), pp. 1117-1129
[25.]
W.C. Tan.
Viruses in asthma exacerbations.
Curr Opin Pulm Med, 11 (2005), pp. 21-26
[26.]
N.G. Papadopoulos, L.A. Stanciu, A. Papi, S.T. Holgate, S.L. Johnston.
A defective type 1 response to rhinovirus in atopic asthma.
Thorax, 57 (2002), pp. 328-332
[27.]
M. Contoli, S.D. Message, V. Laza-Stanca, M.R. Edwards, P.A. Wark, N.W. Bartlett, et al.
Role of deficient type III interferon-lambda production in asthma exacerbations.
Nat Med, 12 (2006), pp. 1023-1026
[28.]
P.A. Wark, S.L. Johnston, F. Bucchieri, R. Powell, S. Puddicombe, V. Laza-Stanca, et al.
Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus.
J Exp Med, 201 (2005), pp. 937-947
[29.]
P.A. Wark, S.L. Johnston, F. Bucchieri, R. Powell, S. Puddicombe, V. Laza-Stanca, et al.
Asthmatic bronchial epithelial cells have deficient innate immune response to infection with rhinovirus.
Lancet, 370 (2007), pp. 1422-1431
[30.]
G.D. Brooks, K.A. Buchta, J.E. Gern, W.W. Busse.
Association of rhinovirus-induced IFN-Á with increased asthma severity.
Am J Respir Crit Care Med, 168 (2003), pp. 1091-1094
[31.]
R.H. Dougherty, J.V. Fahy.
Acute exacerbations of asthma: Epidemiology, biology and the exacerbation-prone phenotype.
Clin Exp Allergy, 39 (2009), pp. 193-202
[32.]
P.A. Wark, P.G. Gibson.
Asthma exacerbations 3: Pathogenesis.
Thorax, 61 (2006), pp. 909-915
[33.]
E. Xystrakis, Z. Urry, C.M. Hawrylowics.
Regulatory T cell therapy as individualized medicine for asthma and allergy.
Curr Opin Allergy Clin Immunol, 7 (2007), pp. 535-541

Both authors have contributed equally to the investigation.

Copyright © 2010. Sociedad Española de Neumología y Cirugía Torácica
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