Topical interleukin 1 receptor antagonist promotes corneal transplant survival
Topical interleukin 1 receptor antagonist promotes corneal transplant survival
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DOI：
10.1097/00007890-199705270-00022
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发表时间：
1997-05-27
期刊：
影响因子：
6.2
通讯作者：
Streilein, JW
中科院分区：
文献类型：
--
作者：
Dana, MR;Yamada, J;Streilein, JW
背景白细胞介素（IL）-1是一种有效的促炎细胞因子，在启动和维持免疫原性炎症中起关键作用。我们进行了一系列的实验，以确定局部应用IL-1受体拮抗剂（IL-1 ra）是否可以延长原位同种异体移植小鼠模型的角膜移植存活。对于所有实验，将C57 BL/6角膜移植到BALB/c（主要组织相容性和次要组织相容性不同）眼中。“高风险”移植是已经缝合到BALB/c受体床上的移植，2周前在宿主角膜中放置三次间断缝合引起角膜新生血管形成。两个风险组均以盲法分为治疗亚组，接受20 mg/ml IL-1 ra与0.2%透明质酸钠溶剂混合（n=28）或仅接受安慰剂（n=25）。所有移植物在手术后8周评估排斥反应的迹象。随访结束后，取角膜组织行Langerhans细胞计数和组织病理学检查。通过分层的Mantel-Haenszel（P=0.02）和KapIan-Meier（P=0.03）生存分析，与未治疗的对照组相比，IL-1 ra治疗组的正常风险和高风险移植的生存率显著增加。此外，与未处理对照组相比，正常和高危IL-1 ra处理移植物的炎症和朗格汉斯细胞浸润均显著减少。局部应用IL-1 ra对提高角膜移植物存活率有显著的积极作用。
Background. Interleukin (IL)-1 is a potent proinflammatory cytokine that plays a critical role in initiating and maintaining immunogenic inflammation. We performed a series of experiments to determine whether the topical application of IL-1 receptor antagonist (IL-1ra) can prolong corneal transplant survival in the murine model of orthotopic allotransplantation.Methods. For all experiments, C57BL/6 corneas were transplanted into BALB/c (major histocompatibility and minor histocompatibility-disparate) eyes. ''High-risk'' transplants were transplants that had been sutured into BALB/c recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 2 weeks earlier. Both risk groups were divided in a masked fashion into treatment subgroups that received either 20 mg/ml of IL-1ra mixed in 0.2% sodium hyaluronate vehicle (n=28) or placebo alone (n=25). All transplants were evaluated for 8 weeks after surgery for signs of rejection. At the end of follow-up, corneal specimens were processed for enumeration of Langerhans cells and histopathological evaluation.Results. Survival rates of both normal-risk and highrisk transplants increased significantly among the IL-1ra-treated animals compared with untreated controls by both stratified Mantel-Haenszel (P=0.02) and KapIan-Meier survival (P=0.03) analyses. Furthermore, both normal- and high-risk IL-1ra-treated grafts had significantly less inflammation and Langerhans cells infiltration compared with untreated controls.Conclusions. Topical treatment with IL-1ra has a significantly positive effect in promoting corneal allograft survival.