Targeting IL-6 in antibody-mediated kidney transplant rejection

Interleukin (IL)-6 is a major pro-inflammatory cytokine and central regulator of innate and adaptive immune responses. Clinical trials testing antibodies against IL-6 or its receptors have demonstrated its involvement in the pathogenesis of several autoimmune and inflammatory disorders and in the sy...

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Detalles Bibliográficos
Autores: Kanbay, Mehmet, Mizrak, Berk, Copur, Sidar, Alper, Ezgi N., Akgul, Sebahat, Ortiz Arduán, Alberto, Susal, Caner
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:dnet:biblosearchi::5b7654b21f8f8bd6b311ec8b058022be
Acceso en línea:https://hdl.handle.net/10486/773580
https://dx.doi.org/10.1093/ckj/sfaf108
Access Level:acceso abierto
Palabra clave:antibody-mediated rejection
canakinumab
interleukin 6
kidney transplantation
tocilizumab
Medicina
Descripción
Sumario:Interleukin (IL)-6 is a major pro-inflammatory cytokine and central regulator of innate and adaptive immune responses. Clinical trials testing antibodies against IL-6 or its receptors have demonstrated its involvement in the pathogenesis of several autoimmune and inflammatory disorders and in the systemic inflammation and anemia associated to kidney failure and also in kidney allograft rejection. Additionally, the anti-IL-6 receptor antibody tocilizumab and the anti-IL-6 antibody clazakizumab have been studied for the treatment of naïve as well as resistant antibody-mediated kidney allograft rejection with mixed results in observational studies and early clinical development. Following promising results with a clazakizumab in a phase 2 placebo-controlled trial, a large phase 3 trial (IMAGINE) was terminated in 2024 for futility at interim analysis. Investigator-initiated clinical development continues in a smaller phase 3 trial testing tocilizumab (INTERCEPT). In this viewpoint article, we evaluate the pathophysiology of IL-6 in antibody-mediated kidney allograft rejection along with the current status of the clinical development of IL-6 targeting therapies for antibody-mediated kidney allograft rejection episodes within the wider frame of IL-6 targeting therapies in kidney failure that are considered the major causes of graft loss in kidney transplantation