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Published ahead of print on December 4, 2003, doi:10.1164/rccm.200307-1024OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 565-572, (2004)
© 2004 American Thoracic Society

Kinetics of Bone Marrow Eosinophilopoiesis and Associated Cytokines after Allergen Inhalation

Sandra C. Dorman, Roma Sehmi, Gail M. Gauvreau, Rick M. Watson, Ronan Foley, Graham L. Jones, Judah A. Denburg, Mark D. Inman and Paul M. O'Byrne

Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to P. M. O'Byrne, M.D., Health Sciences Centre, Room 3W10, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada. E-mail address: obyrnep{at}mcmaster.ca

Allergen inhalation is associated with increased eosinophil/basophil progenitors in bone marrow 24 hours after allergen inhalation. This study examined the kinetics of eosinophilopoiesis in dual (n = 14), compared with isolated early, responders (n = 12). Dual responders, in contrast to isolated early responders, develop significant sputum and blood eosinophilia and prolonged airway hyperresponsiveness. Bone marrow aspirates were taken before and 5, 12, 24, and 48 hours after allergen inhalation. In dual responders, increases in interleukin (IL)-3–responsive progenitors were detected as early as 5 hours after allergen inhalation, and IL-5–responsive progenitors were detected at 12 and 24 hours. No changes were detected in isolated early responders. Bone marrow IL-5 protein levels increased at 12 and 24 hours in dual responders only and these increases correlated with increases in IL-5–responsive progenitors. In addition, bone marrow IFN-{gamma} levels increased in dual responders at 48 hours. These data demonstrate that, in dual responders, there is allergen-induced activation of an eosinophilopoietic process that is rapid and sustained, and a relationship between increased bone marrow IL-5 levels and increased eosinophil production. We propose that after allergen inhalation, time-dependent changes in cytokine levels in the bone marrow control differentiation of eosinophil/basophil progenitors.

Key Words: allergy • cellular differentiation • eosinophils • human • lung




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