Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration

Blood. 2020 Dec 3;136(23):2667-2678. doi: 10.1182/blood.2020005161.


Glucocorticoids are considered first-line therapy in a variety of eosinophilic disorders. They lead to a transient, profound decrease in circulating human eosinophils within hours of administration. The phenomenon of glucocorticoid-induced eosinopenia has been the basis for the use of glucocorticoids in eosinophilic disorders, and it has intrigued clinicians for 7 decades, yet its mechanism remains unexplained. To investigate, we first studied the response of circulating eosinophils to in vivo glucocorticoid administration in 3 species and found that the response in rhesus macaques, but not in mice, closely resembled that in humans. We then developed an isolation technique to purify rhesus macaque eosinophils from peripheral blood and performed live tracking of zirconium-89-oxine-labeled eosinophils by serial positron emission tomography/computed tomography imaging, before and after administration of glucocorticoids. Glucocorticoids induced rapid bone marrow homing of eosinophils. The kinetics of glucocorticoid-induced eosinopenia and bone marrow migration were consistent with those of the induction of the glucocorticoid-responsive chemokine receptor CXCR4, and selective blockade of CXCR4 reduced or eliminated the early glucocorticoid-induced reduction in blood eosinophils. Our results indicate that glucocorticoid-induced eosinopenia results from CXCR4-dependent migration of eosinophils to the bone marrow. These findings provide insight into the mechanism of action of glucocorticoids in eosinophilic disorders, with implications for the study of glucocorticoid resistance and the development of more targeted therapies. The human study was registered at as #NCT02798523.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Bone Marrow / immunology*
  • Bone Marrow / pathology
  • Eosinophils / immunology*
  • Eosinophils / pathology
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / adverse effects*
  • Humans
  • Leukopenia / chemically induced*
  • Leukopenia / immunology*
  • Leukopenia / pathology
  • Macaca mulatta
  • Male
  • Mice
  • Receptors, CXCR4 / immunology*


  • CXCR4 protein, human
  • CXCR4 protein, mouse
  • Glucocorticoids
  • Receptors, CXCR4

Associated data