Inhibition of inflammation by IL-6 blockade in xenotransplantation

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-02-24 DOI:10.1016/j.cyto.2025.156897

Zuzanna Iwanczyk , Hidetaka Hara , David K.C. Cooper , Akihiro Maenaka

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引用次数: 0

Abstract

The inflammatory cytokine interleukin 6 (IL-6) plays a role in both acute and chronic organ allotransplant rejection. Data suggest that IL-6 inhibition may help prevent or reverse rejection, with large multi-center trials now underway. However, the evidence for the benefit of IL-6 inhibitors in xenotransplantation is limited. IL-6 inhibition has been explored in nonhuman-primate models of xenotransplantation, but no clear consensus exists on its efficacy or the best mode of IL-6 inhibition (anti-IL-6 antibodies, or through IL-6 receptor [IL-6R] blockade).

Extra considerations for IL-6 blockade exist in xenotransplantation, as both recipient (human) and xenograft-derived (porcine) IL-6 may play roles. The systemic inflammation seen in xenograft recipients (SIXR) contributes to significant morbidity and mortality for the recipient through coagulation dysfunction and augmentation of the immune response. Anti-IL-6 antibodies (e.g., siltuximab) bind to human IL-6 and prevent IL-6R activation, but do not bind to porcine IL-6, and so have no effect in preventing graft-driven inflammatory processes. In contrast, IL-6R inhibitors (e.g., tocilizumab) inhibit IL-6 activity by blocking binding of human and porcine IL-6 to human IL-6R. Although IL-6R blockade cannot prevent the effect of IL-6 on porcine cells, it probably prevents graft-derived IL-6 from contributing to an inflammatory response in the host.

This review outlines the role of IL-6 in xenotransplantation and discusses mechanisms for inhibiting IL-6 to improve recipient survival.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.