Monoclonal anti-interleukin‐5 treatment suppresses eosinophil but not T‐cell functions
- 1 May 2003
- journal article
- clinical trial
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 21 (5) , 799-803
- https://doi.org/10.1183/09031936.03.00027302
Abstract
Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma.In-vitrodata and animal studies indicate that the T‐helper (Th) type‐2 cell cytokine, interleukin (IL)‐5, plays an important role in eosinophil maturation, differentiation, recruitment, and survival. The objective of this study was to determine whether intravenous treatment with monoclonal anti-IL‐5 would affect the number of peripheral blood eosinophils, their activation status, T‐cell activation or the pattern of Th1 and Th2 cytokine production.Over a period of 6 months, 19 asthmatics were investigated in a double-blind, placebo-controlled, multicentre study with mepolizumab (SB 240563) anti-IL‐5 antibody administered three times. Before each infusion and 12 weeks after the last infusion, peripheral blood leukocytes were examined, qualitative and quantitative distribution of eosinophils and lymphocyte subpopulations, frequencies of IL‐2, ‐3, ‐4, ‐5, -10, -13, interferon‐γ‐producing CD4 T‐cells and serum eosinophil cationic protein (ECP) levels were determined.Treatment with mepolizumab resulted in a marked, rapid and sustained decrease of eosinophil numbers (median values from 300 to 45 per µL) paralleled by decreased levels of serum ECP (median values from 15 to 5 µg·L−1). Distribution of T‐cell subsets and T‐cell cytokine production were not altered during antibody treatment.In conclusion, administration of mepolizumab to asthmatic patients markedly reduces peripheral blood eosinophils without altering the distribution and activation status of lymphocytes.Keywords
This publication has 26 references indexed in Scilit:
- Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsìveness, and the late asthmatic responsePublished by Elsevier ,2001
- The epidemic of allergy and asthmaNature, 1999
- Induction and regulation of the IgE responseNature, 1999
- Increased levels of IL-5 positive peripheral blood eosinophils and lymphocytes in mild asthmatics after allergen inhalation provocationClinical and Experimental Allergy, 1999
- Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity.The Journal of Experimental Medicine, 1996
- Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthmaJournal of Allergy and Clinical Immunology, 1993
- Predominant TH2-like Bronchoalveolar T-Lymphocyte Population in Atopic AsthmaNew England Journal of Medicine, 1992
- Eosinophilic Inflammation in AsthmaNew England Journal of Medicine, 1990
- Recombinant human interleukin 5 is a selective eosinophil chemoattractantEuropean Journal of Immunology, 1989
- Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors.The Journal of Experimental Medicine, 1988