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

Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response
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-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.
0140-6736
2144-2148
Leckie, Margaret J.
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ten Brinke, Anneke
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Khan, Jamey
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Diamant, Zuzana
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O'Connor, Brian J.
b1626f56-46a3-4691-a0c5-64b0e5340f0b
Walls, Christine M.
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Mathur, Ashwini K.
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Cowley, Hugh C.
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Chung, K. Fan
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Djukanovic, Ratko
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Hansel, Trevor T.
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Holgate, Stephen T.
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Sterk, Peter J.
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Barnes, Peter J.
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Leckie, Margaret J.
daf510ac-a547-494a-b325-d9ebe89cce1b
ten Brinke, Anneke
49ec2aa4-bbd9-4d3f-828d-762c5dd6695a
Khan, Jamey
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Diamant, Zuzana
68f5fb05-cb89-4fc3-9208-9adda60bc723
O'Connor, Brian J.
b1626f56-46a3-4691-a0c5-64b0e5340f0b
Walls, Christine M.
bd9384c4-2e31-4cae-b29c-1fe9494dcf57
Mathur, Ashwini K.
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Cowley, Hugh C.
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Chung, K. Fan
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Djukanovic, Ratko
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Hansel, Trevor T.
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Holgate, Stephen T.
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Sterk, Peter J.
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Barnes, Peter J.
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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).

Record type: Article

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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More information

Published date: 2000
Organisations: Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 27220
URI: http://eprints.soton.ac.uk/id/eprint/27220
ISSN: 0140-6736
PURE UUID: 8ddbc67a-fe00-4097-aaba-302186887723
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 28 Apr 2006
Last modified: 16 Aug 2024 01:32

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Contributors

Author: Margaret J. Leckie
Author: Anneke ten Brinke
Author: Jamey Khan
Author: Zuzana Diamant
Author: Brian J. O'Connor
Author: Christine M. Walls
Author: Ashwini K. Mathur
Author: Hugh C. Cowley
Author: K. Fan Chung
Author: Trevor T. Hansel
Author: Peter J. Sterk
Author: Peter J. Barnes

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