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

采用直径3 mm的环钻法将Fisher 344大鼠供体移植物移植到刘易斯大鼠受体，术后通过裂隙灯检查评估移植物。非治疗组中的所有8个移植物在平均10.5 ± 2.5天发生排斥。相比之下，每天肌肉注射5 mg/kg环孢素A，持续14天，在术后随访30天的5个移植物中，有5个移植物的排斥反应得到抑制，尽管较小剂量的2 mg/kg导致4个移植物中的4个移植物在9 - 14天发生排斥反应。环孢素A（2 mg/kg）联合抗ICAM-1单克隆抗体（1 mg/kg）或抗LFA-1单克隆抗体（1 mg/kg）也不能抑制排斥反应。然而，当环孢菌素A（2 mg/kg）与抗ICAM-1和抗LFA-1单克隆抗体同时给予5只大鼠时，仅1只大鼠在18天时观察到移植物排斥，而其他4只大鼠的移植物在30天内保持透明。总之，使用环孢菌素A以及抗ICAM-1和抗LFA-1单克隆抗体的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.