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Reparixin, a CXCR1/2 inhibitor in islet allotransplantation

机译：Remarixin，Islet分征中的CXCR1 / 2抑制剂

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Quality of life in Type 1 diabetic patients may be improved with islet transplantation, but lifelong immunosuppression is required to prevent rejection. Allo-immune response is a key player in graft dysfunction and although the adaptive immune response is well characterized, the effect of the innate immune reaction after transplantation is only recently becoming appreciated. In this study, we address how the innate response affects long-term outcomes in a murine islet allotransplant model. CTLA-4 Ig treatment is known to significantly prolong kidney subcapsular islet allograft survival and enhance glucose tolerance. The combination of CTLA-4 Ig with reparixin, which blocks against inflammatory neutrophil infiltration, yielded no long-term graft survival in an intrahepatic allotransplant model but had similar long-term graft survival in the kidney subcapsular model. Seven days after transplant, serum blood IFN- levels were significantly lower in the CTLA-4 Ig with reparixin treatment group compared to controls. IL-12p70 cytokine levels were increased with combination treatment, a positive modulation of the inflammatory response to the allograft. Furthermore, KC GRO, also known as CXCL1, was decreased in serum 7 d after transplant. Histologically, we found that immune cell infiltrate, CD4+ and CD8+ T cell populations along with both CXCR1+ and CXCR2+ cell populations were decreased within the CTLA-4 Ig and reparixin islet transplant graft. Overall these data provide insight into the down regulation of T-cell recruitment by CTLA-4 Ig and decreased neutrophil activation and recruitment with reparixin after long-term islet graft survival.
机译：1型糖尿病患者的生命质量可以通过胰岛移植改善，但终身免疫抑制需要防止排斥。 Allo-Immune反应是移植物功能障碍的关键球员，尽管适应性免疫应答很好，但在移植后的先天免疫反应的效果最近仅成为欣赏。在这项研究中，我们解决了先天反应如何影响小鼠胰岛同种异体化模型中的长期结果。已知CTLA-4 Ig治疗可显着延长肾脏亚面胰岛同种异体移植物存活率并增强葡萄糖耐受性。 CTLA-4 Ig与remarixin的组合，其阻断炎症性中性粒细胞浸润，在肝内单体化模型中没有在肝内同种异体的模型中产生长期接枝存活，但在肾脏亚面囊模型中具有类似的长期移植物存活。移植后七天，与对照相比，CTLA-4 Ig的CTLA-4 Ig血清血液IFN-水平显着降低。 IL-12P70细胞因子水平随组合处理而增加，对同种异体移植物的炎症反应的阳性调节。此外，在移植后，在血清7d中，kc gro也称为cxcl1。组织学上，在CTLA-4 IG和Remarixin胰岛移植移植物中，我们发现免疫细胞浸润，CD4 +和CD8 + T细胞群以及CXCR1 +和CXCR2 +细胞群。总体而言，这些数据能够深入了解CTLA-4 Ig的T细胞募集的调节，并在长期胰岛移植物存活后降低了中性粒细胞激活和募集性。

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