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

用直径3 mm的环钻将Fisher 344只大鼠供体移植物移植到Lewis大鼠的受体，术后用裂隙灯检查移植物。非治疗组8枚移植物全部排斥，平均10.5±2.5d。环孢素A每日5 mg/kg肌肉注射14天后，5例移植物发生排斥反应，术后随访至30天，而2 mg/kg的小剂量环孢素A 4例术后9~14天出现排斥反应。环孢素A(2 mg/kg)与抗ICAM-1单抗(1 mg/kg)或抗LFA-1单抗(1 mg/kg)联合应用也不能抑制排斥反应。5只大鼠同时应用环孢素A(2 mg/kg)和抗ICAM-1和抗LFA-1单抗时，仅有1只大鼠在18d时观察到移植物排斥反应，其余4只大鼠的移植物在30d后仍保持畅通。综上所述，环孢菌素A与抗ICAM-1和抗LFA-1单抗联合治疗，似乎能够抑制该动物角膜移植模型中的排斥反应。

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.