Vitamin D3 improves the effects of low dose Der p 2 allergoid treatment in Der p 2 sensitized BALB/c mice.

Q2 Medicine
Clinical and Molecular Allergy Pub Date : 2016-08-05 eCollection Date: 2016-01-01 DOI:10.1186/s12948-016-0044-1
Claudia Petrarca, Emanuela Clemente, Valentina Amato, Alessia Gatta, Sara Cortese, Alessia Lamolinara, Cosmo Rossi, Stefania Zanotta, Gianni Mistrello, Roberto Paganelli, Mario Di Gioacchino
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引用次数: 18

Abstract

Background: Airborne allergens can induce an immunological chronic disease characterized by airway hyper responsiveness and inflammation, mediated by exaggerated Th2 immune response. Allergen-specific immunotherapy (AIT) is effective for treating this condition because it is able to modify its natural course by opposing the underlying pathogenic mechanisms and determining immune suppression, immune deviation and tolerance. The rational for the present study was to investigate the possibility of improving allergoid-based IT in terms of efficacy and safety. Recently, 1α,25-dihydroxyvitamin D3 (VD3), the active metabolite of vitamin D3, was described to be a potent inducer of T regulatory cells and to be a good adjuvant in AIT settings.

Methods: We investigated whether the co-administration of VD3 could potentiate the effect of AIT even when added to a low dose of chemically-modified monomeric allergoid of Der p 2 (d2-OID), in a Derp p 2 (d2)-sensitized BALB/c mice model. Control groups where treated with sham, VD3 alone or d2-OID only.

Results: The d2-OID alone was not fully successful, as expected for a low dose. VD3 administration was associated with some valuable, although limited, changes in the immunological parameters in the lung. On the contrary, the VD3 adjuvated allergoid vaccine induced the most prominent reduction of airway eosinophilia and Th2 cytokines and concomitant increase of T regulatory cells and IL-10 in the lung and Der p 2-specific IgG2a in the serum.

Conclusions: The addition of VD3 to a conventional AIT protocol would allow the reduction of allergoid dose needed and therefore, the production costs. Moreover, beneficial immunomodulatory effects have been achieved by the oral administration which might favour the management of the therapy by the patients and their adherence, possibly enhancing the efficacy of the treatment.

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维生素D3可改善Der p2致敏BALB/c小鼠低剂量Der p2类过敏原治疗的效果。
背景:空气传播的过敏原可诱发一种以气道高反应性和炎症为特征的免疫性慢性疾病,由过度的Th2免疫反应介导。过敏原特异性免疫疗法(AIT)能够通过对抗潜在的致病机制和决定免疫抑制、免疫偏差和耐受来改变其自然过程,是治疗这种疾病的有效方法。本研究的目的是从有效性和安全性方面探讨改善基于过敏原的IT的可能性。最近,维生素D3的活性代谢物1α,25-二羟基维生素D3 (VD3)被描述为T调节细胞的有效诱导剂,并且在AIT环境中是一种良好的佐剂。方法:我们研究了在derp2 (d2)致敏的BALB/c小鼠模型中,即使将VD3添加到低剂量的derp2 (d2- oid)化学修饰的单体过敏原中,是否也能增强AIT的作用。对照组分别给予假药、单独使用VD3或仅使用d2-OID。结果:单独使用d2-OID并不完全成功,正如预期的低剂量。VD3给药与肺免疫参数的一些有价值的(尽管有限)变化有关。相反,VD3佐剂的类变应原疫苗诱导的气道嗜酸性粒细胞和Th2细胞因子的减少最为显著,同时肺中T调节细胞和IL-10以及血清中Der p2特异性IgG2a的增加。结论:在常规AIT方案中加入VD3可以减少所需的类过敏原剂量,从而降低生产成本。此外,口服给药已取得有益的免疫调节作用,这可能有利于患者对治疗的管理和他们的依从性,可能提高治疗的疗效。
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来源期刊
Clinical and Molecular Allergy
Clinical and Molecular Allergy Medicine-Immunology and Allergy
CiteScore
8.20
自引率
0.00%
发文量
11
审稿时长
13 weeks
期刊介绍: Clinical and Molecular Allergy is an open access, peer-reviewed, online journal that publishes research on human allergic and immunodeficient disease (immune deficiency not related to HIV infection/AIDS). The scope of the journal encompasses all aspects of the clinical, genetic, molecular and inflammatory aspects of allergic-respiratory (Type 1 hypersensitivity) and non-AIDS immunodeficiency disorders. However, studies of allergic/hypersensitive aspects of HIV infection/AIDS or drug desensitization protocols in AIDS are acceptable. At the basic science level, this includes original work and reviews on the genetic and molecular mechanisms underlying the inflammatory response.
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