Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway.
The role of eosinophils as effector cells in asthma pathogenesis has been questioned since an anti-interleukin (IL)-5 monoclonal antibody (mepolizumab), which depleted blood and sputum eosinophils, failed to inhibit allergen-induced bronchoconstriction and airway hyperresponsiveness. However, the effect of IL-5 blockade on tissue eosinophils was not examined. We sought to determine whether mepolizumab depletes airway tissue eosinophils and their products. Twenty-four patients with mild asthma received three intravenous doses of either 750 mg of mepolizumab or placebo in a randomized, 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, FEV1, and peak flow recordings) between the mepolizumab and placebo-treated groups. 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 antieosinophil strategies are required.
Flood-Page
Patrick T
PT
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, United Kingdom.
Menzies-Gow
Andrew N
AN
Kay
A Barry
AB
Robinson
Douglas S
DS
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004802:Eosinophilia / Q000188:drug therapy* / Q000503:physiopathology*; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C434107:mepolizumab