Endogenous polyclonal anti-IL-1 antibody responses potentiate IL-1 activity during pathogenic inflammation

被引:17
|
作者
Spohn, Gunther [1 ]
Arenas-Ramirez, Natalia [2 ]
Bouchaud, Gregory [2 ,3 ]
Boyman, Onur [2 ]
机构
[1] Cytos Biotechnol, Wagistr 25, CH-8952 Schlieren, Switzerland
[2] Univ Zurich, Univ Zurich Hosp, Dept Immunol, Gloriastr 23, CH-8091 Zurich, Switzerland
[3] INRA, Nantes, France
基金
瑞士国家科学基金会;
关键词
Cytokine; IL-1; beta; antibody; autoantibody; inflammation; inflammatory disease; autoinflammatory disease; CHRONIC MUCOCUTANEOUS CANDIDIASIS; COLONY-STIMULATING FACTOR; B-CELL TOLERANCE; BIOLOGICAL-ACTIVITY; IFN-GAMMA; IN-VIVO; AUTOANTIBODIES; RECEPTOR; CYTOKINE; ALPHA;
D O I
10.1016/j.jaci.2016.09.033
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Particular neutralizing mAbs to certain cytokines act as agonists in vivo through protection of the cytokine's active site and prolongation of its half-life. Although this principle might be useful for targeted immunotherapy, its role in the pathogenesis of inflammation and autoimmunity is unclear. Objective: We sought to determine whether slight, structurally nonrelevant modifications of the prototypic proinflammatory cytokine IL-1 beta during an immune response could elicit polyclonal anti-IL-1 beta antibody responses that modulated IL-1 beta's in vivo activity. Methods: We engineered 2 different IL-1 beta variants, thereby mimicking the process of cytokine modification occurring during inflammation, and conjugated them to virus-like particles, followed by immunization of mice. The resulting polyclonal anti-IL-1 beta antibody responses were assessed by using in vitro and in vivo assays, as well as 2 relevant (auto-)inflammatory murine models. Results: Although antibody responses generated to one variant were potently inhibiting IL-1 beta, antibody responses induced by the other variant even potentiated the in vivo effects of IL-1 beta; the latter led to enhanced morbidity in 2 different IL-1 beta-mediated mouse models, including a model of inflammatory bowel disease and an inflammatory arthritis model. Conclusion: These data demonstrate that endogenous polyclonal anti-cytokine antibody responses can enhance the cytokine's activity in inflammatory and autoimmune diseases.
引用
收藏
页码:1957 / +
页数:12
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