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Role of eosinophils in asthma 

Role of eosinophils in asthma
Chapter:
Role of eosinophils in asthma
Author(s):

Andrew J Wardlaw

DOI:
10.1093/med/9780199651559.003.0081
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date: 22 October 2019

Background: Interleukin-5 (IL-5) is essential for the formation of eosinophils, which are thought to have a major role in the pathogenesis of asthma and other allergic diseases. We aimed to assess the effects of monoclonal antibody to IL-5 on blood and sputum eosinophils, airway hyper-responsiveness, and the late asthmatic reaction to inhaled allergen in patients with mild asthma. Methods: We did a double-blind randomised placebo-controlled trial, in which a single intravenous infusion of humanised (IgG-K) monoclonal antibody to IL-5 (SB-240563) was given at doses of 2.5 mg/kg (n = 8) or 10.0 mg/kg (n = 8). The effects of treatment on responses to inhaled allergen challenge, sputum eosinophils, and airway hyper-responsiveness to histamine were measured at weeks 1 and 4 with monitoring of blood eosinophil counts for up to 16 weeks. Findings: Monoclonal antibody against IL-5 lowered the mean blood eosinophil count at day 29 from 0.25 x 10(9)/L (95% CI 0.16–0.34) in the placebo group to 0.04 x 10(9)/L (0.00–0.07) in the 10 mg/kg group (p < 0.0001), and prevented the blood eosinophilia that follows allergen challenge. After inhaled allergen challenge, 9 days after treatment, the percentage sputum eosinophils were 12.2% in the placebo group and lowered to 0.9% (–1.2 to 3.0; p = 0.0076) in the 10 mg/kg group, and this effect persisted at day 30 after the dose. There was no significant effect of monoclonal antibody to IL-5 on the late asthmatic response or on airway hyper-responsiveness to histamine. Interpretation: A single dose of monoclonal antibody to IL-5 decreased blood eosinophils for up to 16 weeks and sputum eosinophils at 4 weeks, which has considerable therapeutic potential for asthma and allergy. However, our findings question the role of eosinophils in mediating the late asthmatic response and causing airway hyper-responsiveness.

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