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Eur Cytokine Netw. 2018 Jun 1;29(2):48-51. doi: 10.1684/ecn.2018.0410.

Role of IL-18 in transplant biology.

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Department of General Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou City, People's Republic of China.
Department of Laboratory Medicine, the PLA 307 Hospital, Beijing, People's Republic of China.
Intensive Care Unit, Zhejiang Hospital, People's Republic of China.
Department of Thyroid and Breast Surgery, Tongde Hospital of Zhejiang Province, Hangzhou City, People's Republic of China.


Since pro-inflammatory cytokine IL-18 and its receptor (IL-18R) are closely involved in regulating both adaptive and innate immune responses, it is conceivable that they might play an important role in organ transplantation. IL-18 can stimulate lymphocytes to produce the IFN-γ and regulate macrophage activity, thereby increasing the expression of proinflammatory cytokines including IL-1β, IL-6, CCL4 (macrophage inflammatory protein-1 β), CXCL2 (macrophage inflammatory protein-2), and CCL2 (monocyte chemotactic protein-1). Nevertheless, the IL-18 signaling pathway and its underlying mechanisms remain obscure in transplant biology. This review is to summarize recent advances in our knowledge about the IL-18 signaling pathway and to analyze their functions in transplant-related biology. It was found that IL-18/IL-18R signaling pathway contributed to vascular transplantation, ischemmia/reperfusion, acute kidney injury, and acute rejection of kidney/liver/heart transplantation. IL-18 was a potential CYP3A expression modulator and was capable of affecting tacrolimus pharmacokinetics. Neutralizing IL-18 by its inhibitor IL-18 binding protein could efficiently suppress the production of injury-associated cytokines such as IL-6, TNF-α, IFN-γ, CXCL10 (IFN-γ-inducible protein10), and CX3CL1 (fractalkine) and improve allograft function. Blockade of IL-18 signaling could regulate cardiomyocyte apoptosis and inhibit Th17 cells differentiation. Alteration of IL-18 levels was suggested as a biomarker for predicting ongoing allograft outcome. All these activities could deepen our understanding of immunobiological role of IL-18 and its receptor in the field of organ transplantation. Intervention of IL-18 signaling pathway might be utilized as a therapeutic strategy in clinic.


IL-18; inflammatory cytokines; organ transplantation

[Indexed for MEDLINE]

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