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二肽基肽酶-4 抑制剂西他列汀、维达列汀和沙格列汀不会损害固有和适应性免疫反应。

The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses.

机构信息

Division of Clinical Pharmacology, Center of Integrated Protein Science Munich (CIPS-M), Klinikum der Universität München, Munich, Germany; Department of Gastroenterology Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.

出版信息

Diabetes Obes Metab. 2014 Jun;16(6):569-72. doi: 10.1111/dom.12246. Epub 2013 Dec 29.

Abstract

Inhibitors of dipeptidylpeptidase IV (DPP-IV) represent a novel class of frequently used anti-diabetic drugs. In addition to its function in metabolic regulation, DPP-IV also plays a role in the immune system. Whether the DPP-IV inhibitors sitagliptin, vildagliptin or saxagliptin impair immune responses is, however, currently unknown. Here, we investigated the effect of these agents on both innate and adaptive immunity. We found that the DPP-IV inhibitors did not affect the innate immune response induced by Toll-like receptor (TLR) ligands, as cytokine secretion and induction of co-stimulatory molecules by human blood mononuclear cells was not impaired. Furthermore, proliferation of T cells and suppressive function of regulatory T cells was preserved. Mice treated with vildagliptin showed normal cytokine production, immune cell activation and lymphocyte trafficking upon TLR activation. Thus, crucial immunological parameters remain unaffected upon treatment with DPP-IV inhibitors, a fact that is reassuring with respect to safety of these drugs.

摘要

二肽基肽酶 IV(DPP-IV)抑制剂是一类常用于治疗糖尿病的新型药物。除了在代谢调节中的作用外,DPP-IV 还在免疫系统中发挥作用。然而,目前尚不清楚 DPP-IV 抑制剂西他列汀、维格列汀或沙格列汀是否会损害免疫反应。在这里,我们研究了这些药物对固有免疫和适应性免疫的影响。我们发现 DPP-IV 抑制剂不会影响 Toll 样受体(TLR)配体诱导的固有免疫反应,因为人类单核细胞的细胞因子分泌和共刺激分子的诱导不受影响。此外,T 细胞的增殖和调节性 T 细胞的抑制功能得到保留。维格列汀治疗的小鼠在 TLR 激活时表现出正常的细胞因子产生、免疫细胞激活和淋巴细胞迁移。因此,在 DPP-IV 抑制剂治疗下,关键的免疫学参数不受影响,这一事实对于这些药物的安全性是令人放心的。

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