Nicholson, G.C.G.C.NicholsonKariyawasam, H.H.H.H.KariyawasamTan, A.J.A.J.TanHohlfeld, J.M.J.M.HohlfeldQuinn, D.D.QuinnWalker, C.C.WalkerRodman, D.D.RodmanWestwick, J.J.WestwickJurcevic, S.S.JurcevicKon, O.M.O.M.KonBarnes, P.J.P.J.BarnesKrug, N.N.KrugHansel, T.T.T.T.Hansel2022-03-042022-03-042011https://publica.fraunhofer.de/handle/publica/22635410.1016/j.jaci.2011.05.013Background: 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.en610616journal article