Anti-IL-5 (mepolizumab) therapy induces bone marrow eosinophil maturational arrest and decreases eosinophil progenitors in the bronchial mucosa of atopic asthmatics

J Allergy Clin Immunol. 2003 Apr;111(4):714-9. doi: 10.1067/mai.2003.1382.


Background: Eosinophils develop from CD34(+) progenitors under the influence of IL-5. Atopic asthmatic individuals have increased numbers of mature eosinophils and eosinophil pro-genitors within their bone marrow and bronchial mucosa. We have previously reported that anti-IL-5 monoclonal antibody treatment decreases total bone marrow and bronchial mucosal eosinophil numbers in asthma.

Objective: Using an anti-IL-5 monoclonal antibody, we examined the role of IL-5 in eosinophil development within the bone marrow and bronchial mucosa in asthma.

Methods: Blood, bone marrow, and airway mucosal biopsy specimens were examined before and after anti-IL-5 (mepolizumab) treatment of asthmatic individuals in a double-blind, placebo-controlled trial. Numbers of mature and immature eosinophils were measured by histologic stain (bone marrow myelocytes, metamyelocytes, and mature eosinophils), flow cytometry (bone marrow and blood CD34(+)/IL-5Ralpha(+) cells), enumeration of bone marrow-derived eosinophil/basophil colony-forming units in methylcellulose culture, and sequential immunohistochemistry and in situ hybridization (bronchial mucosal CD34(+)/IL-5Ralpha mRNA(+) cells).

Results: Mepolizumab decreased mature eosinophil numbers in the bone marrow by 70% (P =.017) in comparison with placebo and decreased numbers of eosinophil myelocytes and metamyelocytes by 37% (P =.006) and 44% (P =.003), respectively. However, mepolizumab had no effect on numbers of blood or bone marrow CD34(+), CD34(+)/IL-5Ralpha(+) cells, or eosinophil/basophil colony-forming units. There was a significant decrease in bronchial mucosal CD34(+)/IL-5Ralpha mRNA(+) cell numbers in the anti-IL-5 treated group (P =.04).

Conclusion: These data suggest that anti-IL-5 therapy might induce partial maturational arrest of the eosinophil lineage in the bone marrow. The reduction in airway CD34(+)/IL-5 mRNA(+) cell numbers suggests that IL-5 might also be required for local tissue eosinophilopoiesis.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD34 / analysis
  • Asthma / blood
  • Asthma / drug therapy*
  • Bone Marrow Cells / drug effects*
  • Bronchi / drug effects*
  • Double-Blind Method
  • Eosinophils / drug effects*
  • Eosinophils / physiology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Interleukin-5 / analysis


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD34
  • Interleukin-5
  • mepolizumab