Dowling R D, Zenati M, Burckart G J, Yousem S A, Schaper M, Simmons R L, Hardesty R L, Griffith B P
Department of Surgery, University of Pittsburgh, PA 15261.
Surgery. 1990 Aug;108(2):198-204; discussion 204-5.
Current systemic immunosuppressive regimens are unable to prevent lung allograft rejection consistently and are associated with significant morbidity and death. Acute rejection has occurred in 40% and chronic rejection in 50% of our lung recipients. We hypothesized that regional immunotherapy with aerosolized cyclosporine would prevent or reduce lung allograft rejection while allowing for low systemic drug delivery. In a canine model of unilateral lung allotransplantation, aerosolized cyclosporine was delivered directly to the allograft. Acute rejection was prevented or reduced in all treated recipients. All control animals had severe acute rejection. Intragraft cyclosporine concentration was high and systemic drug delivery was low, as evidenced by low whole-blood cyclosporine levels and low tissue cyclosporine levels in skeletal muscle. Ninety-five percent of whole-blood trough cyclosporine levels were less than 150 ng/ml. Aerosolized cyclosporine was able to prevent or reduce acute pulmonary rejection and resulted in minimal systemic drug delivery.
目前的全身性免疫抑制方案无法始终如一地预防肺移植排斥反应，且与显著的发病率和死亡率相关。在我们的肺移植受者中，40%发生了急性排斥反应，50%发生了慢性排斥反应。我们推测，雾化环孢素的局部免疫治疗可以预防或减少肺移植排斥反应，同时实现低剂量的全身性药物输送。在单侧肺同种异体移植的犬模型中，将雾化环孢素直接输送至移植肺。所有接受治疗的受者的急性排斥反应均得到预防或减轻。所有对照动物均发生了严重的急性排斥反应。移植肺内的环孢素浓度较高，而全身性药物输送较低，全血中环孢素水平较低以及骨骼肌组织中环孢素水平较低证明了这一点。95%的全血谷值环孢素水平低于150 ng/ml。雾化环孢素能够预防或减轻急性肺排斥反应，并使全身性药物输送降至最低。
