title: The effects of an anti-IL-13 mAb on cytokine levels and nasal symptoms following nasal allergen challenge.
abstract: 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: NHLI, Imperial College, London, UK.
authors: Grant C
authors: GC
authors: Nicholson
authors: Harsha H
authors: HH
authors: Kariyawasam
authors: Andrew J
authors: AJ
authors: Tan
authors: Jens M
authors: JM
authors: Hohlfeld
authors: Deborah
authors: D
authors: Quinn
authors: Christoph
authors: C
authors: Walker
authors: David
authors: D
authors: Rodman
authors: John
authors: J
authors: Westwick
authors: Stipo
authors: S
authors: Jurcevic
authors: Onn Min
authors: OM
authors: Kon
authors: Peter J
authors: PJ
authors: Barnes
authors: Norbert
authors: N
authors: Krug
authors: Trevor T
authors: TT
authors: Hansel
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D000730:Androstadienes / Q000008:administration & dosage; D018926:Anti-Allergic Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology; D005260:Female; D000068298:Fluticasone; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D031784:Phleum / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D007507:Therapeutic Irrigation
chemical_list: D000305:Adrenal Cortex Hormones; D000485:Allergens; D000730:Androstadienes; D018926:Anti-Allergic Agents; D000911:Antibodies, Monoclonal; D018793:Interleukin-13; D000068298:Fluticasone