IL-6 is a pleiotropic, pro-inflammatory
cytokine that plays an integral role in the development of acute and chronic rejection after solid
organ transplantation. This article reviews the experimental evidence and current clinical application of IL-6/
IL-6 receptor (IL-6R) signaling inhibition for the prevention and treatment of allograft injury.
Recent Findings: There exists a robust body of evidence linking
IL-6 to allograft injury mediated by acute
inflammation, adaptive cellular/humoral responses, innate immunity, and
fibrosis.
IL-6 promotes the
acute phase reaction, induces B cell maturation/antibody formation, directs cytotoxic T-cell differentiation, and inhibits regulatory T-cell development. Importantly, blockade of the IL-6/IL-6R signaling pathway has been shown to mitigate its harmful effects in experimental studies, particularly in models of kidney and heart transplant rejection. Currently, available agents for
IL-6 signaling inhibition include
monoclonal antibodies against
IL-6 or IL-6R and
janus kinase inhibitors. Recent clinical trials have investigated the use of
tocilizumab, an anti-IL-6R mAb, for desensitization and treatment of antibody-mediated rejection (AMR) in kidney transplant recipients, with promising initial results. Further studies are underway investigating the use of alternative agents including
clazakizumab, an anti-IL-6 mAb, and application of
IL-6 signaling blockade to clinical
cardiac transplantation.
Summary: IL-6/IL-6R signaling inhibition provides a novel therapeutic option for the prevention and treatment of allograft injury. To date, evidence from clinical trials supports the use of
IL-6 blockade for desensitization and treatment of AMR in kidney transplant recipients. Ongoing and future clinical trials will further elucidate the role of
IL-6 signaling inhibition in other types of solid
organ transplantation.