BACKGROUND: IL-13 is a key T(H)2 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.
BACKGROUND: IL-13 is a key T(H)2 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.
Authors: Dawn C Newcomb; Madison G Boswell; Matthew M Huckabee; Kasia Goleniewska; Daniel E Dulek; Sara Reiss; Nicholas W Lukacs; Jay K Kolls; R Stokes Peebles Journal: J Immunol Date: 2011-12-30 Impact factor: 5.422
Authors: Dawn C Newcomb; Madison G Boswell; Taylor P Sherrill; Vasiliy V Polosukhin; Kelli L Boyd; Kasia Goleniewska; Steven L Brody; Jay K Kolls; Kenneth B Adler; R Stokes Peebles Journal: Am J Respir Cell Mol Biol Date: 2013-06 Impact factor: 6.914
Authors: David J Jackson; Heidi Makrinioti; Batika M J Rana; Betty W H Shamji; Maria-Belen Trujillo-Torralbo; Joseph Footitt; Aurica G Telcian; Alexandra Nikonova; Jie Zhu; Julia Aniscenko; Leila Gogsadze; Eteri Bakhsoliani; Stephanie Traub; Jaideep Dhariwal; James Porter; Duncan Hunt; Toby Hunt; Trevor Hunt; Luminita A Stanciu; Musa Khaitov; Nathan W Bartlett; Michael R Edwards; Onn Min Kon; Patrick Mallia; Nikolaos G Papadopoulos; Cezmi A Akdis; John Westwick; Matthew J Edwards; David J Cousins; Ross P Walton; Sebastian L Johnston Journal: Am J Respir Crit Care Med Date: 2014-12-15 Impact factor: 21.405