Volume 46, No. 02, Month FEBRUARY, Year 2020, Pages 206 - 212

Changes in tlr 4 expression level and cd14 cd16 monocyte ratio in the peripheral blood of patients with early diabetic nephropathies

Yu Chena,*, Kun Menb, Chun-mei Menga, Jing Maa, Jian-chao Guo

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Cytokine-mediated activation of chronic microinflammatory and nonspecific immune responses plays an important role in the progression of early diabetic nephropathy (EDN). The purpose of this study was to investigate Toll- like receptor 4 (TLR-4) levels in monocytes and the CD14+CD16+ monocyte ratios in peripheral blood from diabetic patients with EDN. One hundred and eighty-eight patients with type 2 diabetes mellitus were recruited and divided into 3 groups according to their microalbumin (mALB) content: (1) A-group (mALB < 30 mg/24 h, n=60); (2) B-group (mALB 30–300 mg/24 h, n=64), which was further divided into the losartan potassium treatment group (B-T-group) and the untreated group (B-NT-group); and (3) C-group (mALB > 300 mg/24 h, n=64). Additionally, samples from 50 healthy patients were collected as the control group (N-group). Immune turbidimetric assays were used to measure high-sensitivity C-reactive protein (hsCRP) levels in serum. The levels of interleukin 6 (IL-6) in serum were detected by ELISA. CD14+CD16+ monocyte ratios and TLR-4 levels in monocytes were assessed by flow cytometry. There was no significant difference in the levels of hsCRP, IL-6, and TLR-4 and the CD14+CD16+ monocyte ratios between the A-group and N-group. The hsCRP, IL-6, TLR-4 and CD14+CD16+ monocyte levels in the B-group and C-group were notably higher than those in the A-group or N-group. Furthermore, compared with levels in the B-NT-group, TLR-4 and CD14+CD16+ monocyte levels were significantly decreased in the B-T-group. TLR-4 and CD14+CD16+ monocyte levels were increased in patients with EDN and restored with losartan potassium treatment, and the monocyte levels were positively correlated with the decrease in mALB. The TLR-4 level in monocyte and CD14+CD16+ monocyte ratio can be used as new targets for the early diagnosis of clinical diabetic nephropathy.


early diabetic nephropathy, TLR-4, CD14+CD16+, chronic immune microinflammation


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