Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions

Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma. In-vitro data 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 obje...

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Published inThe European respiratory journal Vol. 21; no. 5; pp. 799 - 803
Main Authors Buttner, C, Lun, A, Splettstoesser, T, Kunkel, G, Renz, H
Format Journal Article
LanguageEnglish
Published Leeds Eur Respiratory Soc 01.05.2003
Maney
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Abstract Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma. In-vitro data 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-gamma-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 microL) paralleled by decreased levels of serum ECP (median values from 15 to 5 microg x 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.
AbstractList Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma. In-vitro data 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.
Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma. In-vitro data 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-gamma-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 microL) paralleled by decreased levels of serum ECP (median values from 15 to 5 microg x 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.
Author Splettstoesser, T
Lun, A
Renz, H
Buttner, C
Kunkel, G
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Issue 5
Keywords Immune response
Respiratory disease
Treatment efficiency
Cytokine
Monoclonal antibody
Mepolizumab
Eosinophil
Asthma
Immunomodulator
Chemotherapy
Interleukin 5
Treatment
Immunotherapy
T-Lymphocyte
Asthma eosinophils interleukin-5 lymphocytes treatment
Obstructive pulmonary disease
Mechanism of action
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  ident: 2024101810144846000_21.5.799.22
  publication-title: Clin Exp Allergy
  doi: 10.1111/j.1365-2222.1997.tb02984.x
– volume: 164
  start-page: 2142
  year: 2000
  ident: 2024101810144846000_21.5.799.28
  publication-title: J Immunol
  doi: 10.4049/jimmunol.164.4.2142
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Snippet Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma. In-vitro data and animal studies indicate that the T-helper (Th)...
Influx of eosinophils in airway mucosa and airway lumen is a hallmark of bronchial asthma. In-vitro data and animal studies indicate that the T‐helper (Th)...
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SubjectTerms Adult
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized
Asthma - drug therapy
Biological and medical sciences
Blood Proteins - analysis
Blood Proteins - immunology
Double-Blind Method
Eosinophil Granule Proteins
Eosinophils - immunology
Female
Humans
Interleukin-5 - immunology
Lymphocyte Activation - drug effects
Lymphocyte Activation - physiology
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Respiratory system
Ribonucleases
T-Lymphocytes - immunology
Title Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions
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https://www.ncbi.nlm.nih.gov/pubmed/12765424
https://search.proquest.com/docview/73303420
Volume 21
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