Yamada J, Zhu S N, Streilein J W, Dana M R
Laboratory of Immunology, Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4203-8.
Topical treatment with interleukin 1 receptor antagonist (IL-1ra) can promote corneal allograft survival by suppressing induction of allodestructive immunity. The purpose of these experiments was to determine whether IL-1ra could also promote induction of allo-protective tolerogenic pathways, including anterior chamber-associated immune deviation (ACAID), which has been shown to participate in long-term survival of corneal transplants.
Corneal buttons from BALB/c (syngeneic) or C57BL/6 (fully mismatched allogeneic) mice were orthotopically grafted onto BALB/c recipients. Topical IL-1ra or vehicle alone was applied to grafts three times daily. Donor-specific ACAID was measured in allogeneic grafted mice at 4 and 8 weeks after transplantation by ear-challenging grafted hosts with donor-derived splenocytes 1 week after SC immunization. In separate experiments, grafted mice were treated for 4 weeks before injecting ovalbumin (OVA) into their anterior chambers to determine their capacity to induce antigen-specific ACAID.
Treatment with IL-1ra did not promote, or inhibit, induction of donor-specific ACAID compared with vehicle-treated controls at either the early or late time points studied. However, IL-1ra treatment after transplantation led to significantly earlier restoration of the grafted eyes' capacity for inducing ACAID to soluble antigen (OVA).
Promotion of OVA-specific ACAID by IL-1ra suggests that suppression of IL-1-mediated mechanisms contributes to recovery of the anterior segment's immunosuppressive microenvironment at least 1 month earlier than would otherwise be seen after corneal transplantation. However, IL-1ra treatment does not alter induction of donor-specific ACAID after transplantation, suggesting that its anti-inflammatory activities do not lead to an ACAID-inducing signal per se. This suggests that IL-1ra promotes graft survival almost exclusively by virtue of suppressing inflammation and not by directly promoting tolerance or antigen-specific regulatory pathways.
用白细胞介素1受体拮抗剂（IL-1ra）进行局部治疗可通过抑制同种异体破坏性免疫的诱导来促进角膜移植存活。这些实验的目的是确定IL-1ra是否还能促进同种异体保护性耐受途径的诱导，包括前房相关免疫偏离（ACAID），已证明其参与角膜移植的长期存活。
将来自BALB/c（同基因）或C57BL/6（完全不匹配的同种异体）小鼠的角膜纽扣原位移植到BALB/c受体上。每天三次将局部IL-1ra或单独的赋形剂应用于移植物。在移植后4周和8周，通过在皮下免疫1周后用供体来源的脾细胞对移植宿主进行耳部攻击，在同种异体移植小鼠中测量供体特异性ACAID。在单独的实验中，在将卵清蛋白（OVA）注入移植小鼠前房之前，对其进行4周的治疗，以确定它们诱导抗原特异性ACAID的能力。
与赋形剂处理的对照组相比，在研究的早期或晚期时间点，用IL-1ra处理均未促进或抑制供体特异性ACAID的诱导。然而，移植后用IL-1ra治疗导致移植眼诱导对可溶性抗原（OVA）的ACAID的能力显著更早恢复。
IL-1ra对OVA特异性ACAID的促进表明，IL-1介导机制的抑制至少比角膜移植后否则会出现的情况提前1个月有助于眼前段免疫抑制微环境的恢复。然而，IL-1ra治疗不会改变移植后供体特异性ACAID的诱导情况，这表明其抗炎活性本身不会导致诱导ACAID的信号。这表明IL-1ra几乎完全通过抑制炎症而不是直接促进耐受或抗原特异性调节途径来促进移植物存活。
