局部应用白细胞介素-1与肿瘤坏死因子-α阻断剂联合皮质类固醇疗法对小鼠角膜炎症、新生血管形成及移植存活影响的比较（美国眼科学会论文）
Comparison of topical interleukin-1 vs tumor necrosis factor-alpha blockade with corticosteroid therapy on murine corneal inflammation, neovascularization, and transplant survival (an American Ophthalmological Society thesis).
作者信息
Dana Reza
机构信息
Laboratory of Immunology, Schepens Eye Research Institute, and the Cornea Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA.
出版信息
Trans Am Ophthalmol Soc. 2007;105:330-43.
PURPOSE
Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) play critical roles in mediating corneal inflammation. In this study, topical blockade of IL-1 and TNF-alpha, alone or in combination, was compared to conventional corticosteroid anti-inflammatory therapy in suppressing infiltration of the cornea by antigen-presenting Langerhans cells (LCs) and in promoting corneal transplant survival in a mouse model of keratoplasty.
METHODS
Study drugs included topical 2% IL-1 receptor antagonist (IL-1Ra), 1.5% soluble TNF-alpha receptor (sTNFR), and 1% prednisolone phosphate (Pred), all formulated in hyaluronic acid vehicle. Fifty eyes of BALB/c mice were used for LC studies where the numbers of LCs were determined 1 week after electrocautery to the corneal surface or transplantation of C57BL/6 corneas. Additionally, 65 BALB/c mice received corneal allografts and were randomized to receive one of the following for 8 weeks: (1) IL-1Ra, (2) sTNFR, (3) Pred, (4) combined IL-1Ra and Pred, or (5) vehicle alone.
RESULTS
Mean suppression of LC infiltration after electrocautery or transplantation was 67% and 71%, respectively, for IL-1Ra, 40% and 62% for sTNFR, 70% and 72% for sTNFR+IL-1Ra, and 77% and 78% for Pred alone. Rejection rates were 15% for IL-1Ra (P = .01), 38% for sTNFR (P = .1), 17% for Pred (P = .02), and 7% for combined IL-1Ra+Pred (P = .002) as compared to 69% for the vehicle-treated group. IL-1Ra and Pred, but not sTNFR, significantly inhibited post-transplantation neovascularization.
CONCLUSIONS
Topical IL-1Ra and prednisolone are comparable in their capacity to promote graft survival. sTNFR therapy, though effective, has much lower efficacy as compared to IL-1Ra or Pred. Combination IL-1Ra and steroid therapy offers only minimal added efficacy over either agent used alone.
目的
白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）在介导角膜炎症中起关键作用。在本研究中，将单独或联合局部阻断IL-1和TNF-α与传统皮质类固醇抗炎疗法进行比较，以研究其在抑制抗原呈递朗格汉斯细胞（LCs）对角膜的浸润以及促进角膜移植存活方面的作用，该研究采用角膜移植小鼠模型。
方法
研究药物包括局部用2%白细胞介素-1受体拮抗剂（IL-1Ra）、1.5%可溶性肿瘤坏死因子-α受体（sTNFR）和1%磷酸泼尼松龙（Pred），均用透明质酸载体配制。50只BALB/c小鼠的眼睛用于LC研究，在角膜表面电灼或移植C57BL/6角膜1周后测定LC数量。此外，65只BALB/c小鼠接受了同种异体角膜移植，并随机分为以下几组，接受8周的治疗：（1）IL-1Ra，（2）sTNFR，（3）Pred，（4）联合使用IL-1Ra和Pred，或（5）单独使用载体。
结果
电灼或移植后，IL-1Ra对LC浸润的平均抑制率分别为67%和71%，sTNFR为40%和62%，sTNFR + IL-1Ra为70%和72%，单独使用Pred为77%和78%。与载体治疗组的69%相比，IL-1Ra的排斥率为15%（P = 0.01），sTNFR为38%（P = 0.1），Pred为17%（P = 0.02），联合使用IL-1Ra + Pred为7%（P = 0.002）。IL-1Ra和Pred，但不是sTNFR，显著抑制移植后新生血管形成。
结论
局部使用IL-1Ra和泼尼松龙在促进移植物存活的能力方面相当。sTNFR疗法虽然有效，但与IL-1Ra或Pred相比，疗效要低得多。联合使用IL-1Ra和类固醇疗法与单独使用任何一种药物相比，仅提供最小的额外疗效。
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