The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses
The dipeptidylpeptidase-IV inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses
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DOI：
10.1111/dom.12246
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发表时间：
2014-06-01
影响因子：
5.8
通讯作者：
Endres, S.
中科院分区：
文献类型：
--
作者：
Anz, D.;Kruger, S.;Endres, S.
二肽基肽酶IV（DPP-IV）抑制剂是一类新型的常用抗糖尿病药物。除了在代谢调节中的功能外，DPP-IV还在免疫系统中发挥作用。然而，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目前尚不清楚。在这里，我们研究了这些药物对先天性和适应性免疫的影响。我们发现DPP-IV抑制剂不影响Toll样受体（TLR）配体诱导的先天免疫应答，因为细胞因子分泌和人血液单核细胞对共刺激分子的诱导不受损害。此外，保留了T细胞的增殖和调节性T细胞的抑制功能。用维格鲁肽处理的小鼠在TLR活化后显示出正常的细胞因子产生、免疫细胞活化和淋巴细胞运输。因此，关键的免疫学参数在用DPP-IV抑制剂治疗时保持不受影响，这是关于这些药物的安全性的令人放心的事实。
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.