Inhibition of inflammation by IL-6 blockade in xenotransplantation

被引：0
作者：
Iwanczyk, Zuzanna [1 ]
Hara, Hidetaka [2 ]
Cooper, David K. C. [1 ]
Maenaka, Akihiro [1 ]
机构：
[1] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Transplantat Sci, Dept Surg, Boston, MA USA
[2] Yunnan Agr Univ, Coll Vet Med, Kunming, Yunnan, Peoples R China
来源：
CYTOKINE | 2025年 / 189卷
关键词：
IL-6; Inflammation; Pig; Rejection; Xenotransplantation; ANTI-INTERLEUKIN-6 RECEPTOR ANTIBODY; SYSTEMIC INFLAMMATION; RHEUMATOID-ARTHRITIS; MEDIATED REJECTION; T-CELLS; INTERLEUKIN-6; TOCILIZUMAB; CYTOKINE; ACTIVATION; MECHANISMS;
D O I：
10.1016/j.cyto.2025.156897
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 xenograftderived (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, IL6R inhibitors (e.g., tocilizumab) inhibit IL-6 activity by blocking binding of human and porcine IL-6 to human IL6R. 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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页数：9
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