Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response.

来自 dx.doi.org

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作者：

MJ Leckie，AT Brinke，J Khan，Z Diamant，Prof Peter J Barnes

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摘要：

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 hyperresponsiveness, and the late asthmatic reaction to inhaled allergen in patients with mild asthma. 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. Monoclonal antibody against IL-5 lowered the mean blood eosinophil count at day 29 from 0·25x10 9/L (95% CI 0·16-0·34) in the placebo group to 0·04x10 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 hyperresponsiveness to histamine. 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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关键词：

Humans Sputum Asthma Histamine Bronchial Provocation Tests Infusions, Intravenous Analysis of Variance Interleukin-5 Antibodies, Monoclonal Double-Blind Method