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The clinical features of EBV-positive diffuse large B cell lymphoma (DLBCL) indicate a poorer prognosis than EBV-negative DLBCL. Currently, there is no efficacious drug for EBV-positive DLBCL. The cytokine interleukin-21 (IL-21) has been reported to be pro-apoptotic in DLBCL cell lines and is being explored as a new therapeutic strategy for this type of lymphomas. However, our previous studies showed that IL-21 stimulation of EBV-positive DLBCL cell lines leads to increased proliferation. Here, analysis of a rare clinical sample of EBV-positive DLBCL, in combination with a NOD/SCID mouse xenograft model, confirmed the effect of IL-21 on the proliferation of EBV-positive DLBCL cells. Using RNA-sequencing, we identified the pattern of differentially-expressed genes following IL-21 treatment and verified the expression of key genes at the protein level using western blotting. We found that IL-21 upregulates expression of the host MYC and AP-1 (composed of related Jun and Fos family proteins) and STAT3 phosphorylation, as well as expression of the viral LMP-1 protein. These proteins are known to promote the G1/S phase transition to accelerate cell cycle progression. Furthermore, in NOD/SCID mouse xenograft model experiments, we found that IL-21 treatment increases glucose uptake and angiogenesis in EBV-positive DLBCL tumours. Although more samples are needed to validate these observations, our study reconfirms the adverse effects of IL-21 on EBV-positive DLBCL, which has implications for the drug development of DLBCL.

Metabolic syndrome (MetS), one of the major public health concerns, is regarded as the “common soil” of incidence of common chronic diseases and may increase the risk of type 2 diabetes. The predominant underlying mechanism of MetS is insulin resistance (IR). Additionally, previous studies have indicated that IGFBP7 has high affinity of binding with insulin and might induce IR. The objective of this study was to firstly evaluate the associations of serum IGFBP7 levels with IR and MetS with a relatively large sample and population based design. In a population based MetS case-control study, HOMA-IR was used to evaluate the insulin sensitivity and serum IGFBP7 levels were determined with chemiluminescence–linked immunoassay. As a result, the subjects of MetS and IR had higher serum levels of IGFBP7 than control healthy subjects. High serum IGFBP7 levels increased the risk of MetS and IR. Serum IGFBP7 levels were also found to be significantly correlated with metabolic-associated parameters of Waist-to-hip ratio (WHR), HDL and LDL. These findings suggest that serum IGFBP7 levels are associated with IR and MetS, providing new insight into the mechanism of IR and Mets. IGFBP7 may be a potential interventional target for IR and Mets.