Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience

Ther Adv Respir Dis. 2017 Jan;11(1):40-45. doi: 10.1177/1753465816673303. Epub 2016 Nov 17.

Abstract

Eosinophils represent approximately 1% of peripheral blood leukocytes in normal donors and their maturation and differentiation in the bone marrow are mainly regulated by interleukin (IL)-5 [Broughton et al. 2015]. IL-5, a cytokine that belongs to the β common-chain family, together with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulates also the activation and survival of eosinophils and, to some extent, of basophils. IL-5 binds to a heterodimer receptor composed of the specific subunit IL-5Rα and a common subunit βc shared with IL-3 and GM-CSF. Human eosinophils express approximately a three-fold higher level of IL-5Rα compared with basophils. Major sources of IL-5 are T-helper 2 (Th2) cells, mast cells, CD34+ progenitor cells, invariant natural killer (NK) T-cells, group 2 innate lymphoid cells (ILC2s), and eosinophils themselves. ILC2s control not only eosinophil number but also their circadian cycling through the production of IL-5.

Keywords: IL-5; asthma; eosinophilia; exacerbations; mepolizumab; personalized medicine; severe asthma; targeted therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / physiopathology
  • Eosinophilia / drug therapy*
  • Eosinophilia / immunology
  • Eosinophils / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interleukin-3 / immunology
  • Interleukin-5 / immunology
  • Receptors, Interleukin-5 / immunology
  • Severity of Illness Index

Substances

  • Antibodies, Monoclonal, Humanized
  • Interleukin-3
  • Interleukin-5
  • Receptors, Interleukin-5
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • mepolizumab