Transplantation represents the optimal treatment of choice for end-stage solid organ failure [1]. The dissection of the mechanism of host immunoregulation to allografts and introducing immunosuppressants into clinical practice, which have abated the risk of acute rejection and increased the one-year survival rate of grafts over 85 %[2], [3]. However, current immunosuppressive agents are associated with an unacceptably high risk of multiple side effects, including lethal infectious, cardiovascular, renal, metabolic complications and malignancy [4], [5]. It has been proven that cyclosporine-based immunosuppressive therapy was accompanied with higher occurrence of renal function damage, infection and tumors [6]. Researchers are looking into the potential for novel immunosuppressive medicines for these reasons.

IL-37 is a newly discovered factor of the IL-1 family in recent years. Unlike other members of the IL-1 family, it displayed potential anti-inflammatory and immune suppressive effects [7]. Scientists transfected mouse macrophages with human derived IL-37, which resulted in a reduction of pro-inflammatory cytokines induced by Toll-like receptors (TLRs). In addition, the use of siRNA to silence endogenous IL-37 in human blood mononuclear cells led to an increase in the release of pro-inflammatory cytokines. Those for the first time demonstrated the anti-inflammatory properties of IL-37 [8]. In the mouse colitis model, compared with wild-type mice, the secretions of IL-1β, IFN-γ and TNF-α were reduced, and the expression of IL-10 was upregulated in IL-37tg mice [9]. Meanwhile, Luo et al proved that dendritic cells (DCs) from IL to 37tg mice demonstrated a lower ability to stimulate naive T cells and antigen-specific T cells, but enhanced the induction of Tregs [10]. The inhibitory effect of IL-37 in the STAT or NF-κB signaling pathway after binding to the receptor IL-18Ra and IL-1R8 (SIGIRR) may be the basis for its anti-inflammatory and immunomodulatory effects [11]. Although injection of recombinant human (rh) IL-37 could alleviate endotoxemia, acute lung injury, spinal cord injury, asthma and myocardial infarction in mice, whether it could alleviate allograft rejection has not been fully elucidated [12].

We speculate that IL-37 may be a promising candidate for prevention of allograft rejection. The objective of this research is to identify the role of IL-37 and investigate the novel therapeutic strategy that would allow minimize rejection and improve graft survival.