Banner N R, Yacoub M H
Royal Brompton and Harefield NHS Trust, Harefield Hospital, Harefield Middx UB9 6JH, UK.
Transplant Proc. 2004 Mar;36(2 Suppl):302S-308S. doi: 10.1016/j.transproceed.2004.01.031.
The discovery of cyclosporine proved to be a breakthrough that helped transform the status of both heart and lung transplantation from experimental to established therapeutic procedures. Cyclosporine inhibits the early phase of T-cell activation and thus of the alloimmune response. It proved to be highly effective in prophylaxis against acute rejection but its use has been limited by dose-related renal toxicity. Consequently, it has generally been used in regimens that combine it with other immunosuppressive agents with the aim of preventing acute rejection while minimising toxicity. For many years 'triple therapy' using cyclosporine, azathioprine and corticosteroids was the most commonly used regimen for both heart and lung transplantation. Other agents have now become available that provide more effective prophylaxis against acute rejection than azathioprine; these include, mycophenolate and the TOR inhibitors sirolimus and everolimus. Everolimus has also been shown to inhibit the early phase of cardiac allograft vasculopathy. Unfortunately, the TOR inhibitors also potentiate the nephrotoxicity of cyclosporine. Both mycophenolate and the TOR inhibitors are subject to pharmacokinetic interactions with cyclosporine. We are now entering a new phase of clinical immunosuppression where we need to learn how to best combine the agents that are currently available to provide the safest and most effective immunosuppression for patients undergoing heart or lung transplantation.
环孢素的发现被证明是一项突破，它有助于将心脏和肺移植的地位从实验性治疗程序转变为既定的治疗方法。环孢素抑制T细胞活化的早期阶段，从而抑制同种免疫反应。它在预防急性排斥反应方面被证明非常有效，但其使用受到剂量相关肾毒性的限制。因此，它通常被用于与其他免疫抑制剂联合使用的方案中，目的是预防急性排斥反应，同时将毒性降至最低。多年来，使用环孢素、硫唑嘌呤和皮质类固醇的“三联疗法”是心脏和肺移植最常用的方案。现在有其他药物可供使用，它们在预防急性排斥反应方面比硫唑嘌呤更有效；这些药物包括霉酚酸酯和TOR抑制剂西罗莫司和依维莫司。依维莫司也已被证明可抑制心脏同种异体移植血管病变的早期阶段。不幸的是，TOR抑制剂也会增强环孢素的肾毒性。霉酚酸酯和TOR抑制剂都与环孢素有药代动力学相互作用。我们现在正进入临床免疫抑制的新阶段，在这个阶段，我们需要学习如何最好地联合目前可用的药物，为接受心脏或肺移植的患者提供最安全、最有效的免疫抑制。
