Yamada J, Dana M R, Zhu S N, Alard P, Streilein J W
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Mass 02114, USA.
Arch Ophthalmol. 1998 Oct;116(10):1351-7. doi: 10.1001/archopht.116.10.1351.
To delineate the mechanisms by which topical interleukin 1 receptor antagonist (IL-1RA) treatment promotes orthotopic corneal allograft survival.
Corneal buttons were prepared from eyes of C57BL/6 mice and placed orthotopically in normal or neovascularized (high-risk) eyes of BALB/c mouse recipients. Topical IL-1RA (or vehicle alone) was applied to grafts 3 times daily until the grafted eyes were enucleated. Corneal specimens were evaluated for content of Langerhans cells. A week after enucleation, 1 group of recipients was tested for allospecific delayed-type hypersensitivity elicited by intrapinnae injections of donor splenocytes. In companion experiments, a second group of mice that underwent transplantation, IL-1RA treatment, and enucleation was challenged with orthotopic skin grafts from B10.D2 donor mice (sharing minor H antigens with C57BL/6 mice) to determine whether the second group of mice could reject grafts bearing corneal donor minor H alloantigens in an accelerated fashion.
Mice whose orthotopic corneal allografts were treated topically with IL-1RA acquired neither donor-specific delayed-type hypersensitivity (P<.001) nor the capacity to reject orthotopic donor-type skin allografts in an accelerated manner (P<.05), whereas controls treated with vehicle alone developed delayed-type hypersensitivity and rejected B10.D2 grafts in an accelerated manner. Moreover, IL-1RA-treated grafts placed in both high-risk (P = .01) and normal-risk (P = .004) eyes displayed significantly reduced levels of infiltrating Langerhans cells compared with vehicle-treated controls.
Topical IL-1RA promotes corneal allograft survival in large part by preventing activity of recipient Langerhans cells, and thereby preventing these cells from inducing systemic allosensitization. These data suggest that IL-1 plays a key role in promoting allosensitization when corneal allografts are placed orthotopically.
Suppression of allosensitization by topical IL-1RA may prove a clinically useful method for enhancing corneal transplant survival.
阐明局部应用白细胞介素1受体拮抗剂（IL-1RA）治疗促进原位角膜移植存活的机制。
从C57BL/6小鼠眼中制备角膜植片，并原位植入BALB/c小鼠受体的正常或新生血管化（高风险）眼中。每天3次向移植物局部应用IL-1RA（或仅用赋形剂），直至摘除移植眼。评估角膜标本中朗格汉斯细胞的含量。摘除眼球1周后，对1组受体进行耳内注射供体脾细胞引发的同种异体特异性迟发型超敏反应检测。在平行实验中，对另一组接受移植、IL-1RA治疗和眼球摘除的小鼠，用B10.D2供体小鼠（与C57BL/6小鼠共享次要组织相容性抗原）的原位皮肤移植物进行攻击，以确定该组小鼠是否能以加速方式排斥带有角膜供体次要组织相容性同种异体抗原的移植物。
原位角膜移植局部应用IL-1RA治疗的小鼠既未获得供体特异性迟发型超敏反应（P<0.001），也未获得以加速方式排斥原位供体型皮肤移植物的能力（P<0.05），而仅用赋形剂治疗的对照组出现迟发型超敏反应，并以加速方式排斥B10.D2移植物。此外，与赋形剂治疗的对照组相比，置于高风险（P = 0.01）和正常风险（P = 0.004）眼中的IL-1RA治疗移植物浸润的朗格汉斯细胞水平显著降低。
局部应用IL-1RA主要通过阻止受体朗格汉斯细胞的活性，从而防止这些细胞诱导全身同种异体致敏，来促进角膜移植存活。这些数据表明，原位植入角膜移植物时，IL-1在促进同种异体致敏中起关键作用。
局部应用IL-1RA抑制同种异体致敏可能是提高角膜移植存活率的一种临床有用方法。
