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Published ahead of print on October 17, 2002, doi:10.1164/rccm.200208-789OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 2, January 2003, 199-204

A more recent version of this article appeared on January 15, 2003
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Submitted on August 8, 2002
Accepted on October 16, 2002

Anti-IL-5 (mepolizumab) only partially depletes eosinophils from asthmatic airway tissue

Patrick T Flood-Page1, Andrew N Menzies-Gow1, Barry Kay1*, and Douglas S Robinson1

1 Allergy, Imperial College, London, United Kingdom

* To whom correspondence should be addressed. E-mail: a.b.kay{at}ic.ac.uk.

Rationale. The role of eosinophils as effector cells in asthma pathogenesis has been questioned since an anti-IL-5 monoclonal antibody (mepolizumab), which depleted blood and sputum eosinophils, failed to inhibit allergen induced bronchoconstriction and airways hyperresponsiveness. However, the effect of IL-5 blockade on tissue eosinphils was not examined. Objectives. We sought to determine whether mepolizumab depletes airway tissue eosinophils and their products. Main findings. 24 mild asthmatics received three intravenous doses of either 750mg of mepolizumab, or placebo, in a randomised, double blind, parallel group fashion over 20 weeks. Mepolizumab produced a median decrease from baseline of 55% for airway eosinophils (interquartile range 29-89%, p=0.009 versus placebo), 52% for bone marrow eosinophils (45-76%, p=0.003) and 100% for blood eosinophils (range 67-100%, p=0.02). Mepolizumab had no appreciable effect on bronchial mucosal staining of eosinophil major basic protein. There were no significant changes in clinical measures of asthma (airway hyperresponsiveness, forced expiratory volume in one second and peak flow recordings) between the mepolizumab and placebo treated groups. Principal conclusions. Anti-IL-5 treatment reduces, but does not deplete airway or bone marrow eosinophils. The role of the eosinophil remains uncertain. Further clinical studies in asthma with more effective anti-eosinophil strategies are required.
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