Effect of inhaled interleukin-5 on eosinophil progenitors in the bronchi and bone marrow of asthmatic and non-asthmatic volunteers.
BACKGROUND
Asthma is characterized by increases in mature eosinophils and their progenitors within the bronchus and bone marrow. IL-5 plays a key role in eosinophil development in the bone marrow and at the site of allergic inflammation. We therefore studied the effects of nebulized IL-5 on eosinophils, their progenitors and in situ haemopoiesis within the airway and bone marrow.


METHODS
Nine atopic asthmatics and 10 non-atopic non-asthmatic control volunteers inhaled 10 microg of IL-5 or placebo via a nebulizer in a double-blind, randomized, cross-over study. Bronchoscopy, bone marrow aspiration and peripheral blood sampling were performed 24 h after nebulization. Four weeks later, volunteers inhaled the alternative solution and underwent a repeat bronchoscopy and bone marrow aspiration.


RESULTS
Inhalation of IL-5 significantly decreased CD34(+)/IL-5Ralpha mRNA(+) cells within the bronchial mucosa and the percentage of CD34(+) cells that were CCR3(+) within the bone marrow of atopic asthmatic, but not control, volunteers. Inhalation of IL-5 also induced a significant increase in bronchial mucosal eosinophils in the non-atopic non-asthmatic control volunteers, but not in the asthmatics. IL-5 had no effect on spirometry or airways hyper-reactivity in either group.


CONCLUSIONS
Inhaled IL-5 modulated eosinophil progenitor numbers in both the airways and bone marrow of asthmatics and induced local eosinophilia in non-asthmatics.
Menzies-Gow
A N
AN
Leukocyte Biology Section, National Heart & Lung Institute, Imperial College, London, UK.
Flood-Page
P T
PT
Robinson
D S
DS
Kay
A B
AB
D000280:Administration, Inhalation; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D001249:Asthma / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005541:Forced Expiratory Volume; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D015848:Interleukin-5 / Q000008:administration & dosage / Q000378:metabolism*; D053666:Interleukin-5 Receptor alpha Subunit / Q000032:analysis / Q000235:genetics; D007958:Leukocyte Count; D008875:Middle Aged; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D012720:Severity of Illness Index
D018952:Antigens, CD34; C515350:CCR3 protein, human; C508599:IL5 protein, human; C485918:IL5RA protein, human; D015848:Interleukin-5; D053666:Interleukin-5 Receptor alpha Subunit; D012333:RNA, Messenger; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins