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

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-kappa) 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 towered the mean blood eosinophil count at day 29 from 0 . 25x10(9)/L (95% Cl 0 . 16-0 . 34) in the placebo group to 0 . 04x10(9)/L (0 . 00-0 . 07) in the 10 mg/kg group (p<00001), 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.