Original Article
Subject Categories: Immunology/Infection
Journal of Investigative Dermatology (2004) 122, 1406–1412; doi:10.1111/j.0022-202X.2004.22619.x
Intravenous Anti-IL-5 Monoclonal Antibody Reduces Eosinophils and Tenascin Deposition in Allergen-Challenged Human Atopic Skin
Simon Phipps, Patrick Flood-Page, Andrew Menzies-Gow, Yee Ean Ong and AB Kay
Department of Allergy and Clinical Immunology, Imperial College London, NHLI Division, London, UK
Correspondence: A. B. Kay, Department of Allergy and Clinical Immunology, Imperial College London, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK Email: a.b.kay@imperial.ac.uk
Received 30 October 2003; Revised 30 January 2004; Accepted 16 February 2004.
Abstract
Anti-IL-5 monoclonal antibody (mepolizumab) reduces baseline bronchial mucosal eosinophils and deposition of extracellular matrix proteins in the reticular basement membrane in mild asthma. Here we report the effect of anti-IL-5, in the same patients, on allergen-induced eosinophil accumulation, tenascin deposition (as a marker of repair and remodelling) and the magnitude of the late-phase allergic cutaneous reaction. Skin biopsies were performed in 24 atopic subjects at allergen- and diluent-injected sites before 6 and 48 h after, three infusions of a humanized, monoclonal antibody against IL-5 (mepolizumab) using a randomized double-blind, placebo-controlled design. Anti-IL-5 significantly inhibited eosinophil infiltration in 6 h and 48 h skin biopsies as well as the numbers of tenascin immunoreactive cells at 48 h. In contrast, anti-IL-5 had no significant effect on the size of the 6 or 48 h late-phase cutaneous allergic reaction. This study (a) suggests that eosinophils are unlikely to cause the redness, swelling, and induration characteristic of the peak (6 h) late-phase cutaneous allergic reaction and (b) shows that decreases in tenascin positive cells at 48 h correlates with reduction of eosinophils, so providing further evidence of involvement in remodelling processes associated with allergic inflammation.
Keywords:
anti-IL-5, eosinophil, late-phase reaction, skin, tenascin
Abbreviations:
APAAP, alkaline phosphatase anti-alkaline phosphatase; ECM, extracellular matrix; FEV1, forced expiratory volume in 1 s; IL, interleukin; LPR, late-phase reaction; MBP, major basic protein; TGF-
, transforming growth factor-
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