IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys

被引：74

作者：

Bree, Andrea ^{[1
]}

Schlerman, Franklin J. ^{[1
]}

Wadanoli, Michael ^{[1
]}

Tchistiakova, Lioudmila ^{[1
]}

Marquette, Kimberly ^{[1
]}

Tan, Xiang-Yang ^{[1
]}

Jacobson, Bruce A. ^{[1
]}

Widom, Angela ^{[1
]}

Cook, Timothy A. ^{[1
]}

Wood, Nancy ^{[1
]}

Vunnum, Suresh ^{[1
]}

Krykbaev, Rustem ^{[1
]}

Xu, Xin ^{[1
]}

Donaldson, Debra D. ^{[1
]}

Goldman, Samuel J. ^{[1
]}

Sypek, Joseph ^{[1
]}

Kasaian, Marion T. ^{[1
]}

机构：

[1] Wyeth Ayerst Res, Cambridge, MA 02140 USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2007年 / 119卷 / 05期

关键词：

cytokines; inflammation; cynomolgus monkey; asthma; Ascaris suum;

D O I：

10.1016/j.jaci.2007.02.009

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Airway inflammation is a hallmark feature of asthma and a driver of airway hyperresponsiveness. IL-13 is a key inducer of airway inflammation in rodent models of respiratory disease, but a role for IL-13 has not been demonstrated in primates. Objective: We sought to test the efficacy of a neutralizing antibody to human IL-13 in a cynomolgus monkey model of lung inflammation. Methods: Using cynomolgus monkeys (Macaca fascicularis) that are sensitized to Ascaris suum through natural exposure, we developed a reproducible model of acute airway inflammation after segmental A suum antigen challenge. This model was used to test the in vivo efficacy of mAb13.2, a mouse mAb directed against human IL-13, and IMA-638, the humanized counterpart of mAb13.2. Bronchoalveolar lavage (BAL) cells and BAL fluid were collected before and after antigen challenge and assayed for cellular content by means of differential count. Results: Total BAL cell count, eosinophil number, and neutrophil number were all reduced in animals treated with mAb13.2 or IMA-638 compared with values in control animals that were untreated, given saline, or treated with human IgG of irrelevant specificity. In addition, levels of eotaxin and RANTES in BAL fluid were reduced in anti-IL-13-treated animals compared with levels seen in control animals. Conclusion: These findings support a role for IL-13 in maintaining lung inflammation in response to allergen challenge in nonhuman primates.

引用

页码：1251 / 1257

页数：7

共 38 条

[21] Role of interleukin-13 in eosinophil accumulation and airway remodelling in a mouse model of chronic asthma [J].