Effects of Anticytokine Therapy in a Mouse Model of Chronic Asthma
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Kumar, Rakesh K; Herbert, John; Webb, Dianne; Li, Lily; Foster, Paul S
Description
The relative contribution of Th2 and Th1 cytokines to the pathogenesis of lesions of chronic asthma remains poorly understood. To date, therapeutic inhibition of Th2 cytokines has proved disappointing. We used a clinically relevant model of chronic allergic asthma in mice to compare the effects of administering neutralizing antibodies to interleukin (IL)-13, IL-5, and interferon-γ (IFN-γ) to animals with established disease. As has been observed in clinical studies, anti-IL-5 inhibited both...[Show more]
dc.contributor.author | Kumar, Rakesh K | |
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dc.contributor.author | Herbert, John | |
dc.contributor.author | Webb, Dianne | |
dc.contributor.author | Li, Lily | |
dc.contributor.author | Foster, Paul S | |
dc.date.accessioned | 2015-12-13T23:07:37Z | |
dc.identifier.issn | 1073-449X | |
dc.identifier.uri | http://hdl.handle.net/1885/86287 | |
dc.description.abstract | The relative contribution of Th2 and Th1 cytokines to the pathogenesis of lesions of chronic asthma remains poorly understood. To date, therapeutic inhibition of Th2 cytokines has proved disappointing. We used a clinically relevant model of chronic allergic asthma in mice to compare the effects of administering neutralizing antibodies to interleukin (IL)-13, IL-5, and interferon-γ (IFN-γ) to animals with established disease. As has been observed in clinical studies, anti-IL-5 inhibited both inflammation and remodeling but had no effect on airway responsiveness to methacholine. Anti-IL-13 effectively suppressed eosinophil recruitment and accumulation of chronic inflammatory cells in the airways. This treatment also partially suppressed changes of airway wall remodeling, including goblet cell hyperplasia/metaplasia and subepithelial fibrosis, but had limited ability to inhibit airway hyperreactivity (AHR). In contrast, treatment with anti-IFN-γ markedly suppressed AHR. This antibody inhibited accumulation of chronic inflammatory cells but did not affect eosinophil recruitment or changes of remodeling. We conclude that inhibition of IL-5 is beneficial and that inhibition of IL-13 has considerable potential as a therapeutic strategy in chronic asthma, that IFN-γ may play an important role in the pathogenesis of AHR, and that co-operative interaction between Th2 and Th1 cytokines contributes to the pathogenesis of the lesions of chronic asthma. | |
dc.publisher | American Thoracic Society | |
dc.source | American Journal of Respiratory and Critical Care Medicine | |
dc.subject | Keywords: ammonium sulfate; beta gl 113; c 531; cytokine antibody; gamma interferon; gamma interferon antibody; interleukin 13; interleukin 13 antibody; interleukin 5; interleukin 5 antibody; methacholine; monoclonal antibody; protein antibody; r 46a2; trfk 5; uncl Airway remodeling; Bronchial hyperreactivity; Interferon-?; Interleukin-13; Interleukin-5 | |
dc.title | Effects of Anticytokine Therapy in a Mouse Model of Chronic Asthma | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.description.refereed | Yes | |
local.identifier.citationvolume | 170 | |
dc.date.issued | 2004 | |
local.identifier.absfor | 110701 - Allergy | |
local.identifier.ariespublication | MigratedxPub15113 | |
local.type.status | Published Version | |
local.contributor.affiliation | Kumar, Rakesh K, University of New South Wales | |
local.contributor.affiliation | Herbert, John, University of California | |
local.contributor.affiliation | Webb, Dianne, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Li, Lily, University of Newcastle | |
local.contributor.affiliation | Foster, Paul S, College of Medicine, Biology and Environment, ANU | |
local.description.embargo | 2037-12-31 | |
local.bibliographicCitation.startpage | 1043 | |
local.bibliographicCitation.lastpage | 1048 | |
local.identifier.doi | 10.1164/rccm.200405-681OC | |
dc.date.updated | 2016-02-24T09:47:22Z | |
local.identifier.scopusID | 2-s2.0-8444245228 | |
Collections | ANU Research Publications |
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