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

Leckie, Margaret J., ten Brinke, Anneke, Khan, Jamey, Diamant, Zuzana, O'Connor, Brian J., Walls, Christine M., Mathur, Ashwini K., Cowley, Hugh C., Chung, K. Fan, Djukanovic, Ratko, Hansel, Trevor T., Holgate, Stephen T., Sterk, Peter J. and Barnes, Peter J. (2000) Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. The Lancet, 356 (9248), 2144-2148. (doi:10.1016/S0140-6736(00)03496-6).

Abstract

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 hyperresponsiveness, 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 0·25x109/L (95% CI 0·16-0·34) in the placebo group to 0·04x109/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.
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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Contributors

Author: Ratko Djukanovic

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