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 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.
Büttner
C
C
Dept of Clinical Immunology and Asthma Outpatient Dept, Charité, Campus Virchow-Klinikum, Humboldt-Universität, Berlin.
Lun
A
A
Splettstoesser
T
T
Kunkel
G
G
Renz
H
H
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy; D001798:Blood Proteins / Q000032:analysis / Q000276:immunology; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012260:Ribonucleases; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; C434107:mepolizumab; D012260:Ribonucleases