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 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.


RESULTS
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 hyper-responsiveness to histamine.


CONCLUSIONS
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.
Leckie
M J
MJ
National Heart and Lung Institute, Imperial College, London, UK.
ten Brinke
A
A
Khan
J
J
Diamant
Z
Z
O'Connor
B J
BJ
Walls
C M
CM
Mathur
A K
AK
Cowley
H C
HC
Chung
K F
KF
Djukanovic
R
R
Hansel
T T
TT
Holgate
S T
ST
Sterk
P J
PJ
Barnes
P J
PJ
D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000628:therapy*; D001985:Bronchial Provocation Tests; D004311:Double-Blind Method; D004804:Eosinophils / Q000378:metabolism*; D006632:Histamine / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D007958:Leukocyte Count; D008297:Male; D013183:Sputum / Q000166:cytology
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D006632:Histamine