Open Access

REVIEW

Role of IL-18 in transplant biology

Chen Liu^1,a, Juntao Chen^1,a, Baoqing Liu^1,a, Shunzong Yuan^2,a, Dawei Shou³, Liang Wen¹, Xiaoying Wu⁴, Weihua Gong¹

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

* Corresponding Author: Weihua Gong,

European Cytokine Network 2018, 29(2), 48-51. https://doi.org/10.1684/ecn.2018.0410

Accepted 08 June 2018;

Abstract

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.

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Keywords

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