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Published ahead of print on December 4, 2003, doi:10.1164/rccm.200307-1024OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 5, March 2004, 565-572

A more recent version of this article appeared on March 1, 2004
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Submitted on July 28, 2003
Accepted on November 23, 2003

The Kinetics of Bone Marrow Eosinophilopoiesis and Associated Cytokines After Allergen Inhalation

Sandra C Dorman1, Roma Sehmi1, Gail M Gauvreau1, Rick M Watson1, Ronan Foley1, Graham L Jones1, Judah A Denburg1, Mark D Inman1, and Paul M O'Byrne1*

1 Medicine, McMaster University, Firestone Institute for Respiratory Health, Hamilton, Ontario, Canada

* To whom correspondence should be addressed. E-mail: obyrnep{at}mcmaster.ca.

Allergen inhalation is associated with increased eosinophil/basophil progenitors in bone marrow 24 hours post-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 IL-3-responsive progenitors were detected as early as 5 hours post-allergen, and IL-5-responsive progenitors 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. Additionally, bone marrow IFN-{gamma} levels increased in dual responders at 48hours. These data demonstrate that, in dual responders, there is: an allergen-induced activation of an eosinophilopoietic process which is rapid and sustained and; a relationship between increased bone marrow IL-5 levels and increased eosinophil production. We propose that following allergen inhalation, time-dependent changes in cytokine levels in the bone marrow control differentiation of eosinophil/basophil progenitors.
Key words: Human, Eosinophils, Cellular differentiation, Allergy, Lung




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