New Agents

Mepolizumab, a monoclonal antibody against interleukin-5 that depletes blood and sputum eosinophils, has failed to inhibit airway hyperresponsiveness. To study the effect of mepolizumab on tissue eosinophils, Flood-Page and coworkers did a double-blind study in 24 patients with mild asthma over 20 weeks. Three intravenous doses of mepolizumab produced a 55% decrease in airway eosinophils, a 52% decrease in bone marrow eosinophils, and a 100% decrease in blood eosinophils. Mepolizumab had no appreciable effect on staining for eosinophil major basic protein in bronchial mucosa, FEV₁, or airway hyperresponsiveness. The authors conclude that the relatively modest depletion of airway eosinophils by an antibody directed against interleukin-5 and residual evidence of eosinophil degranulation may explain the minimal clinical effects of the antibody in patients with asthma. An editorial commentary by Busse and Kelly accompanies this article.

In 26 patients with severe persistent asthma being treated with oral or high-dose inhaled glucocorticoids, Kips and coworkers did a double-blind randomized trial of increasing doses of an antibody directed against interleukin-5 (SCH55700). Intravenous administration of the antibody achieved dose-dependent decreases in circulating eosinophils. Eosinophils remained depressed at 30 days after a dose of 1 mg per kg: 0.07 versus 0.23 x 10⁹ per liter at baseline. Administration of 0.3 mg per kg produced a significant increase in FEV₁ at 24 hours. Adverse effects were not noted. The authors conclude that SCH55700 is a biologically active antibody against interleukin-5 that can be safely used in patients with severe asthma. An editorial commentary by Kay and Menzies-Gow accompanies this article.

Citations 1-4 of 4 total displayed.

Eosinophils and Interleukin-5: The Debate Continues

A. Barry Kay and Andrew Menzies-Gow
Am. J. Respir. Crit. Care Med. 167: 1586-1587. [Full text]

Effect of SCH55700, a Humanized Anti-Human Interleukin-5 Antibody, in Severe Persistent Asthma: A Pilot Study

Johan C. Kips, Brian J. O'Connor, Stephen J. Langley, Ashley Woodcock, Huib A. M. Kerstjens, Dirkje S. Postma, Mel Danzig, Francis Cuss, and Romain A. Pauwels
Am. J. Respir. Crit. Care Med. 167: 1655 -1659. First published online as doi:10.1164/rccm.200206-525OC [Abstract] [Full text]

Is the Eosinophil a "Humpty Dumpty" Cell in Asthma?

William W. Busse and Elizabeth A. E. B. Kelly
Am. J. Respir. Crit. Care Med. 167: 102-103. [Full text]

Eosinophil's Role Remains Uncertain as Anti–Interleukin-5 only Partially Depletes Numbers in Asthmatic Airway

Patrick T. Flood-Page, Andrew N. Menzies-Gow, A. Barry Kay, and Douglas S. Robinson
Am. J. Respir. Crit. Care Med. 167: 199 -204. First published online as doi:10.1164/rccm.200208-789OC [Abstract] [Full text]

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