Monoclonal Antibodies to ICAM-1 and LFA-1 Prolong Corneal Allograft Survival in Rats

将Fisher 344大鼠供体移植至Lewis大鼠受体，采用直径为3mm的环钻，术后裂隙灯检查评估移植情况。非治疗组8例移植物平均排斥时间为10.5 + 2.5天。相比之下，肌肉注射5mg /kg环孢素A，连续14天，术后随访30天的5例移植中有5例排斥反应被抑制，尽管较小剂量的2mg /kg在9至14天的4例移植中有4例出现排斥反应。环孢素A （2mg/kg）与抗icam -1单克隆抗体（1mg/kg）或抗lfa -1单克隆抗体（1mg/kg）联用也未能抑制排斥反应。然而，当5只大鼠同时给予环孢素A （2mg/kg）抗icam -1和抗lfa -1单克隆抗体时，只有1只大鼠在18天出现了排斥反应，而其他4只大鼠的移植物在30天内保持清晰。综上所述，在该动物角膜移植模型中，环孢素A与抗icam -1和抗lfa -1单克隆抗体联合治疗似乎能够抑制排斥反应。

Fisher 344 rat donor grafts were transplanted to Lewis rat recipients using 3 mm diamter trephination, and the grafts were assessed postoperatively by slit lamp examination. All 8 grafts in a non-treatment group rejected at a mean of 10.5 + 2.5 days. In contrast, intramuscular injection of 5 mg/kg cyclosporin A daily for 14 days resulted in suppression of rejection in 5 of 5 grafts that were followed up to 30 days postoperatively, although a lesser dose of 2 mg/kg resulted in rejection at 9 to 14 days in 4 of 4 grafts. Cyclosporin A (2mg/kg), combined with either anti-ICAM-1 monoclonal antibody (1mg/kg) or anti-LFA-1 monoclonal antibody (1mg/kg), also failed to suppress rejection. However, when cyclosporin A (2mg/kg) was administered with both anti-ICAM-1 and anti-LFA-1 monoclonal antibodies in 5 rats, graft rejection was observed in only 1 rat at 18 days, while the grafts in the other 4 rats remained clear up to 30 days. In conclusion, combination therapy using cyclosporin A,and both anti-ICAM-1 and anti-LFA-1 monoclonal antibodies, appears capable of suppressing rejection in this animal corneal transplant model.