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PMID: 14523040 Published · ppublish English Clinical Trial Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics.

The Journal of clinical investigation ·Vol. 112 ·No. 7 ·2003-10-00 ·Pages 1029-36

Flood-Page P, Menzies-Gow A, Phipps S, Ying S, Wangoo A, Ludwig MS, Barnes N, Robinson D, Kay AB

Abstract

Eosinophil-derived TGF-beta has been implicated in remodeling events in asthma. We hypothesized that reduction of bronchial mucosal eosinophils with anti-IL-5 would reduce markers of airway remodeling. Bronchial biopsies were obtained before and after three infusions of a humanized, anti-IL-5 monoclonal antibody (mepolizumab) in 24 atopic asthmatics in a randomized, double-blind, placebo-controlled study. The thickness and density of tenascin, lumican, and procollagen III in the reticular basement membrane (RBM) were quantified immunohistochemically by confocal microscopy. Expression of TGF-beta1 mRNA by airway eosinophils was assessed by in situ hybridization, and TGF-beta1 protein was measured in bronchoalveolar lavage (BAL) fluid by ELISA. At baseline, airway eosinophil infiltration and ECM protein deposition was increased in the RBM of asthmatics compared with nonasthmatic controls. Treating asthmatics with anti-IL-5 antibody, which specifically decreased airway eosinophil numbers, significantly reduced the expression of tenascin, lumican, and procollagen III in the bronchial mucosal RBM when compared with placebo. In addition, anti-IL-5 treatment was associated with a significant reduction in the numbers and percentage of airway eosinophils expressing mRNA for TGF-beta1 and the concentration of TGF-beta1 in BAL fluid. Therefore eosinophils may contribute to tissue remodeling processes in asthma by regulating the deposition of ECM proteins.

MeSH Terms
Antibodies, Monoclonal/therapeutic use Antibodies, Monoclonal, Humanized Asthma/metabolism,therapy Basement Membrane/metabolism Bronchi/metabolism Chondroitin Sulfate Proteoglycans/analysis Collagen Type III/analysis Double-Blind Method Eosinophils/physiology Extracellular Matrix Proteins/metabolism Humans Immunohistochemistry Interleukin-5/antagonists & inhibitors Keratan Sulfate/analysis Lumican RNA, Messenger Tenascin/analysis Transforming Growth Factor beta Transforming Growth Factor beta1
Chemicals
Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Chondroitin Sulfate Proteoglycans Collagen Type III Extracellular Matrix Proteins Interleukin-5 LUM protein, human Lumican RNA, Messenger TGFB1 protein, human Tenascin Transforming Growth Factor beta Transforming Growth Factor beta1 Keratan Sulfate mepolizumab
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Flood-Page Patrick
Department of Allergy and Clinical Immunology, Imperial College London, National Heart and Lung Institute, London, United Kingdom.
Menzies-Gow Andrew
Phipps Simon
Ying Sun
Wangoo Arun
Ludwig Mara S
Barnes Neil
Robinson Douglas
Kay A Barry
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI17974
Published
2003-10-00
Pages
1029-36
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC198522
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI17974 PMC Full Text View journal details
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