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The effects of an anti-IL-13 mAb on cytokine levels and nasal symptoms following nasal allergen challenge

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Grant C Nicholson, Harsha H Kariyawasam, Andrew J Tan, Jens M Hohlfeld, Deborah Quinn, Christoph Walker, David Rodman, John Westwick, Stipo Jurcevic, Onn Min Kon, Peter J Barnes, Norbert Krug, Trevor T Hansel

Original languageEnglish
Pages (from-to)800-807.e9
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume128
Issue number4
DOIs
PublishedOct 2011

King's Authors

Abstract

Background
IL-13 is a key TH2 cytokine that is implicated in allergic responses.

Objective
We evaluated the effects of an anti–IL-13–blocking antibody compared with placebo on repeated nasal allergen challenge responses in hay fever patients out of season.

Methods
We performed a parallel group double-blind study of anti–IL-13 (single dose, 6 mg/kg intravenously, n = 16) and placebo (n = 15), with an additional open label group given a topical nasal corticosteroid (n = 5). Subjects received intranasal timothy grass pollen (Phleum pratense P5 allergen), and serial samples of nasal mucosal lining fluid were taken by using synthetic absorptive matrix and by nasal lavage.

Results
Administration of anti–IL-13 on day 1 resulted in a significant decrease in IL-13 levels in synthetic absorptive matrix eluates compared with placebo (area under the curve 0-8 hours, change from baseline) during the late phase after nasal allergen challenge on day 5 (P < .05) and day 7 (P < .01). There were no apparent effects of anti–IL-13 treatment on nasal lavage eosinophil numbers or total nasal symptom scores versus placebo. However, in a subgroup with high late-phase IL-13 levels at screening, there was a trend for a decrease in total nasal symptom scores after nasal allergen challenge on day 5, when compared with subjects with low IL-13 levels (P < .10). Nasal fluticasone caused suppression of IL-13 (P < .05 on day 5) as well as IL-5 (P < .01 on day 5) levels in the late phase compared with placebo.

Conclusions
Anti–IL-13 had specific pharmacodynamic action in this nasal allergen challenge model, causing profound inhibition of nasal lining fluid IL-13 responses. In addition, there was a possible effect of anti–IL-13 treatment on total nasal symptom scores in a subgroup with high late-phase nasal IL-13 levels at screening.

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