Critical Roles for Interleukin-4 and Interleukin-5 during Respiratory Syncytial Virus Infection in the  Development of Airway Hyperresponsiveness after  Airway Sensitization

Schwarze, Jürgen; Cieslewicz, Grzegorz; Joetham, Anthony; Ikemura, Toshihide; Mäkelä, Mika; Dakhama, Azzeddine; Shultz, Leonard D.; Lamers, Marinus C.; Gelfand, Erwin W.

doi:10.1164/ajrccm.162.2.9903057

Cited by 77 publications

(52 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, T cells possess functional IL-4 but not IL-13 receptors. The fact that IL-4 had the most effect (even though this was a modest one) is consistent both with experimental observations in murine models in which a critical role for IL-4 in development of airway hyperresponsiveness was found, with overexpression of IL-4 delaying clearance of RSV (38,39). The lack of effect of IL-10 was somewhat unexpected inasmuch as endogenous IL-10 increases during clinical RSV infection (40) and has been associated with subsequent development of recurrent wheezing (41).…”

Section: Discussionsupporting

confidence: 86%

Steroids Fail to Down-Regulate Respiratory Syncytial Virus-Induced IL-8 Secretion in Infants

THOMAS¹

2002

Pediatric Research

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 86%

Steroids Fail to Down-Regulate Respiratory Syncytial Virus-Induced IL-8 Secretion in Infants

THOMAS¹

2002

Pediatric Research

View full text Add to dashboard Cite

“…IFN-␥ production is restricted to T cells and NK cells. Although produced in large amounts in the lungs of RSV-infected adult mice, IFN-␥ did not appear to be involved in the development of AHR (40). The present study provides additional evidence that IFN-␥ is not involved in the development of AHR.…”

Section: Discussionmentioning

confidence: 41%

The Enhancement or Prevention of Airway Hyperresponsiveness during Reinfection with Respiratory Syncytial Virus Is Critically Dependent on the Age at First Infection and IL-13 Production

Dakhama

Park

Taube

et al. 2005

The Journal of Immunology

Self Cite

130

161

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) infection in early life is suspected to play a role in the development of postbronchiolitis wheezing and asthma. Reinfection is common at all ages, but factors that determine the development of altered airway function after reinfection are not well understood. This study was conducted in a mouse model to define the role of age in determining the consequences on airway function after reinfection. Mice were infected shortly after birth or at weaning and were reinfected 5 wk later, followed by assessment of airway function, airway inflammation, and lung histopathology. Infection of mice at weaning elicited a protective airway response upon reinfection. In this age group, reinfection resulted in increased airway inflammation, but without development of airway hyperresponsiveness (AHR) or eosinophilia and decreased IL-13 levels. By contrast, neonatal infection failed to protect the airways and resulted in enhanced AHR after reinfection. This secondary response was associated with the development of airway eosinophilia, increased IL-13 levels, and mucus hyperproduction. Both CD4- and CD8-positive T cells were a source of IL-13 in the lung, and inhibition of IL-13 abolished AHR and mucus production in these mice. Inoculation of UV-inactivated virus failed to elicit these divergent responses to reinfection, emphasizing the requirement for active lung infection during initial exposure. Thus, neonatal RSV infection predisposes to the development of airway eosinophilia and enhanced AHR via an IL-13-dependent mechanism during reinfection, whereas infection at a later age protects against the development of these altered airway responses after reinfection.

show abstract

“…In contrast, IFN-c, the predominant cytokine in acute RSV infection, did not seem to be required for the development of AHR in the mouse model used. On the contrary, the presence of IFN-c appeared to be somewhat protective against these consequences of RSV infection [64].…”

Section: Immune Responses Elicited By Respiratory Syncytial Virusmentioning

confidence: 96%

“…However, in the experiments by SCHWARZE et al [63] IFN-c did not seem to be involved in the development of AHR and airway inflammation in acute RSV infection. Their studies indicate that IL-5 is critical for RSV-induced enhancement of lung eosinophilia and AHR in response to allergic airway sensitization [64]. The presence of IL-4 also seems essential for the development of AHR after RSV infection and subsequent allergic airway sensitization, possibly by enhancing IL-5 production [64].…”

Section: Immune Responses Elicited By Respiratory Syncytial Virusmentioning

confidence: 99%

“…Their studies indicate that IL-5 is critical for RSV-induced enhancement of lung eosinophilia and AHR in response to allergic airway sensitization [64]. The presence of IL-4 also seems essential for the development of AHR after RSV infection and subsequent allergic airway sensitization, possibly by enhancing IL-5 production [64]. In contrast, IFN-c, the predominant cytokine in acute RSV infection, did not seem to be required for the development of AHR in the mouse model used.…”

Section: Immune Responses Elicited By Respiratory Syncytial Virusmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases

Wennergren¹,

Kristjánsson²

2001

European Respiratory Journal

View full text Add to dashboard Cite

Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases. G. Wennergren, S. Kristjánsson. #ERS Journals Ltd 2001. ABSTRACT: Evidence from a large number of prospective case-control studies shows that respiratory syncytial virus (RSV) bronchiolitis in infancy is often associated with recurrent wheezing and asthma during subsequent years. However, wheezing tends to diminish and most studies show no significant increase in wheezing compared to controls by school age or adolescence. An unresolved question is whether severe RSV infection during infancy causes the respiratory sequelae or inherent abnormalities predispose an infant to develop severe respiratory infection and sequelae, i.e. RSV is associated with the development of pulmonary sequelae.Studies on long-term outcome of RSV bronchiolitis are reviewed from an evidencebased perspective.The majority of prospective placebo-controlled studies do not show any long-term beneficial effects of corticosteroid treatment, i.e. the risk of subsequent wheezing is not diminished by the treatment. The evidence for an increased risk of allergic sensitization after RSV bronchiolitis is not nearly as strong as the evidence for an increased risk of subsequent wheezing. In fact, most studies do not show any significant increase in atopy after RSV bronchiolitis. This suggests that the increased risk of wheezing after RSV is not linked to an increased risk of atopy. There are some indications that infants who develop severe RSV and subsequent wheezing may have aberrations that predate the RSV infection.To decide whether respiratory syncytial virus bronchiolitis causes, or is associated with the respiratory sequelae (or with subsequent allergy), it will be necessary to conduct prospective, randomized studies, where the cytokine profile prior to bronchiolitis onset is known. Such studies should preferably include some form of intervention against respiratory syncytial virus. A more complete understanding of the risk factors for severe respiratory syncytial virus infection and the role of respiratory syncytial virus infection in the initiation of asthma is needed as a basis for large-scale and cost-effective programmes to prevent respiratory syncytial virus-related morbidity. Eur Respir J 2001; 18: 1044-1058. Respiratory syncytial virus (RSV) bronchiolitis is the most common, severe lower respiratory tract infection in infancy. It now seems well established that RSV bronchiolitis in infancy is associated with recurrent wheezing and asthma during the first decade of life. In some children, wheezing after early lower airway infection with RSV is transient, but in many of the children RSV-induced bronchiolitis represents the onset of asthma. In fact, there are results which indicate that severe RSV bronchiolitis in the young infant may shift the T-helper (Th)1/Th2 balance in favour of a Th2 cytokine pattern, leading to development of allergic sensitization and persistent asthma [1,2]. However, the association with risk of development of atopy...

show abstract

Critical Roles for Interleukin-4 and Interleukin-5 during Respiratory Syncytial Virus Infection in the Development of Airway Hyperresponsiveness after Airway Sensitization

Cited by 77 publications

References 30 publications

Steroids Fail to Down-Regulate Respiratory Syncytial Virus-Induced IL-8 Secretion in Infants

Steroids Fail to Down-Regulate Respiratory Syncytial Virus-Induced IL-8 Secretion in Infants

The Enhancement or Prevention of Airway Hyperresponsiveness during Reinfection with Respiratory Syncytial Virus Is Critically Dependent on the Age at First Infection and IL-13 Production

Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases

Contact Info

Product

Resources

About