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The effects of an anti-IL-13 mAb on cytokine levels and nasal symptoms following nasal allergen challenge
: Nicholson, G.C.; Kariyawasam, H.H.; Tan, A.J.; Hohlfeld, J.M.; Quinn, D.; Walker, C.; Rodman, D.; Westwick, J.; Jurcevic, S.; Kon, O.M.; Barnes, P.J.; Krug, N.; Hansel, T.T.
|The journal of allergy and clinical immunology : JACI 128 (2011), No.4, pp.800-807.e9|
| Journal Article|
|Fraunhofer ITEM ()|
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.