Interferon Lambda Modulates Proinflammatory Cytokines Production in PBMCs from Patients with Chronic Kidney Disease.

Background: CKD is a major cause of morbidity and mortality worldwide. Considerable evidence now indicates that renal inflammation plays a central role in the initiation and progression of CKD. Recent investigations have demonstrated that IFN lambda plays an important role in the pathogenesis of autoimmune and inflammatory diseases. However, the association of IFN lambda with CKD is still poorly understood.Objective: To analyze the correlation between IFN lambda levels and pro-inflammatory cytokines, and to investigate the effect of IFN lambda on PBMCs in patients with CKD.Methods: PBMCs were harvested from patients with CKD and healthy controls for measuring the expression level of inflammatory cytokines by RT-qPCR. Spearman correlation test was used to analyze correlation between IFN lambda and cytokines as well as eGFR. PBMCs from healthy individuals and CKD patients were subjected to IFN lambda protein stimulation. IL6, TNF alpha, IL10, ISG15 and MX1 mRNA level were measured by RT-PCR, STAT1 and phosphorylated STAT1 protein level were measured by Western blot.Results: Patients with CKD showed higher levels of IFN lambda in PBMCs compared to healthy controls. IFN lambda mRNA levels were associated with cytokines and eGFR. The transcription of IL6, TNF alpha, and IL10 was significantly increased in healthy human PBMCs after IFN lambda stimulation. In addition, IFN lambda acts on PBMCs by p-STAT1 and ISG15 as well as MX1.Conclusion: High expression of IFN lambda was found in CKD patients and was associated with eGFR and disease -related cytokines. More importantly, IFN lambda promoted the expression of pro-inflammatory cytokines in PBMCs, suggesting a potential pro-inflammatory role of IFN lambda in CKD.