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Purpose of the Review <p>The proinflammatory Interleukin-6 (IL-6) plays a critical role in immune-mediated allograft rejection. Therapeutic targeting of IL-6 has emerged as a novel strategy in the treatment of rejection in the clinic. Herein, we summarize recent approaches utilizing IL-6 targeted therapies in clinical organ transplantation.&#xa0;</p> Recent Findings <p> Two therapeutic agents, Tocilizumab and Clazakizumab (IL-6 receptor and IL-6 monoclonal antibodies, respectively), were used for either desensitization or for AMR treatment. Most studies were in kidney transplant recipients, in addition to fewer heart and lung transplant recipients. While some studies demonstrated favorable outcomes including improved graft function, reduced antibody levels, and improved histopathological features of rejection following Tocilizumab or Clazakizumab administration, other studies did not demonstrate any beneficial effects. There remains lack of consensus on approaches employing IL-6-targeting in combination with currently used immunosuppression. Mixed results obtained maybe attributed to small number of patients studied, associated co-morbidities and variability in biodistribution among transplant patients.&#xa0;</p> Summary <p> Experimental and clinical evidence support therapeutic targeting of IL-6 in transplant recipients. Widespread adoption will require controlled evaluation in randomized clinical trials to validate long-term outcome and potential side effects.</p>

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Recent Developments in Therapeutic Targeting of Interleukin-6 in Clinical Solid Organ Transplantation

  • 期刊论文

  • 发表日期：

    2026年4月10日

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  • Hiroki Ueda,
  • Mohamed Abdullah,
  • Tara Richards,
  • Lien Casto,
  • Masahiko Kubo,
  • Julie A. Phillippi,
  • David Kaczarawoski,
  • Mohamed B. Ezzelarab

摘要

Purpose of the Review

The proinflammatory Interleukin-6 (IL-6) plays a critical role in immune-mediated allograft rejection. Therapeutic targeting of IL-6 has emerged as a novel strategy in the treatment of rejection in the clinic. Herein, we summarize recent approaches utilizing IL-6 targeted therapies in clinical organ transplantation. 

Recent Findings

Two therapeutic agents, Tocilizumab and Clazakizumab (IL-6 receptor and IL-6 monoclonal antibodies, respectively), were used for either desensitization or for AMR treatment. Most studies were in kidney transplant recipients, in addition to fewer heart and lung transplant recipients. While some studies demonstrated favorable outcomes including improved graft function, reduced antibody levels, and improved histopathological features of rejection following Tocilizumab or Clazakizumab administration, other studies did not demonstrate any beneficial effects. There remains lack of consensus on approaches employing IL-6-targeting in combination with currently used immunosuppression. Mixed results obtained maybe attributed to small number of patients studied, associated co-morbidities and variability in biodistribution among transplant patients. 

Summary

Experimental and clinical evidence support therapeutic targeting of IL-6 in transplant recipients. Widespread adoption will require controlled evaluation in randomized clinical trials to validate long-term outcome and potential side effects.