Document Detail

Critical roles for interleukin-4 and interleukin-5 during respiratory syncytial virus infection in the development of airway hyperresponsiveness after airway sensitization.
MedLine Citation:
PMID:  10934057     Owner:  NLM     Status:  MEDLINE    
In mice, respiratory syncytial virus (RSV) infection can enhance the consequences of allergic airway sensitization, resulting in lung eosinophilia and the development of airway hyperresponsiveness (AHR) to inhaled methacholine (MCh). To delineate a role for interleukin-5 (IL-5), interleukin-4 (IL-4), and interferon gamma (IFN-gamma) in mediating the effects of RSV infection on subsequent allergic sensitization, we treated BALB/c mice with anti-IL-5 during acute RSV infection but not during subsequent exposure to ovalbumin (OVA). IL-5-deficient and IL-4-deficient mice were also treated with IL-5 either during acute RSV infection or during the sensitization period. Airway responsiveness to inhaled MCh was assessed and numbers of lung eosinophils were monitored. Anti-IL-5 treatment during RSV infection reduced AHR and lung eosinophilia after subsequent exposure to allergen. In IL-5-deficient or IL-4-deficient mice lung eosinophilia and AHR after RSV infection and allergen exposure were also markedly reduced. IL-5 administration during RSV infection restored the responses to allergen in both IL-5- and IL-4-deficient mice. However, IL-5 administration only during sensitization restored these responses in IL-4-deficient but not in IL-5-deficient animals. IFN-gamma-deficient mice developed AHR and some lung eosinophilia after allergen exposure alone and when RSV infection preceded allergen, these responses were enhanced. We conclude that both IL-5, particularly during acute infection, and IL-4 are critical in mediating the effects of RSV infection on allergic airway sensitization, resulting in the development of AHR and lung eosinophilia.
J Schwarze; G Cieslewicz; A Joetham; T Ikemura; M J Mäkelä; A Dakhama; L D Shultz; M C Lamers; E W Gelfand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  162     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-09-15     Completed Date:  2000-09-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  380-6     Citation Subset:  AIM; IM    
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.
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MeSH Terms
Interferon-gamma / physiology
Interleukin-4 / pharmacology,  physiology*
Interleukin-5 / pharmacology,  physiology*
Methacholine Chloride
Mice, Inbred BALB C
Ovalbumin / immunology
Pulmonary Eosinophilia / etiology
Respiratory Hypersensitivity / etiology*
Respiratory Syncytial Virus Infections / etiology*,  physiopathology
Grant Support
Reg. No./Substance:
0/Interleukin-5; 207137-56-2/Interleukin-4; 62-51-1/Methacholine Chloride; 82115-62-6/Interferon-gamma; 9006-59-1/Ovalbumin

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