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

详细信息    查看全文

• 作者：Grant C.  ; Nicholson BSc^a ; Harsha H.  ; Kariyawasam MBBS ; PhD^a ; Andrew J.  ; Tan MSc^a ; Jens M.  ; Hohlfeld MD^b ; Deborah  ; Quinn MD^c ; Christoph  ; Walker PhD^c ;   ; ^&dagger ; ; David  ; Rodman MD^c ; John  ; Westwick PhD^c ; Stipo  ; Jurcevic PhD^d ; Onn Min  ; Kon MD^a ; Peter J.  ; Barnes FMedSci ; FRS^a ; Norbert  ; Krug MD^b ; Trevor T.  ; Hansel MBBCh ; PhD^a ;   ; ^{t.hansel@imperial.ac.uk}
• 关键词：Allergic rhinitis ; nasal allergen challenge ; anti&ndash ; IL-13 ; mAb
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：October 2011
• 年：2011
• 卷：128
• 期：4
• 页码：800-807.e9
• 全文大小：1769 K

文摘

Background

IL-13 is a key T_H2 cytokine that is implicated in allergic responses.

Objective

We evaluated the effects of an anti¨CIL-13¨Cblocking 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¨CIL-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¨CIL-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¨CIL-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¨CIL-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¨CIL-13 treatment on total nasal symptom scores in a subgroup with high late-phase nasal IL-13 levels at screening.