SP400EFFECT OF CHOLECALCIFEROL SUPPLEMENTATION ON TLR7, TLR9, IL-6 AND IFN-Y EXPRESSION IN B AND T LYMPHOCYTES ON CHRONIC DIALYSIS PATIENTS

Abstract

Introduction and Aims: Vitamin D deficiency is highly prevalent among patients in all stages of CKD. Previous studies have reported that the Vitamin D deficiency is associated with all causes of mortality and morbidity in CKD patients, which may be linked to an excessive inflammatory state. Toll‐like receptors (TLRs) are involved in several immunologic responses and in others diseases, the expression of this receptors can be modulated by vitamin D. However, the impact of low levels of vitamin D on lymphocytes from CKD patients is unclear. Thus, the purpose of this study was evaluate the effect of cholecalciferol treatment on IL‐6, IFN‐y TLR‐7 and TLR‐9 expression in lymphocytes B and T in patients on chronic dialysis with vitamin D hipovitaminosis. Methods: In a randomized, placebo‐controlled, double‐blind study, we investigated the effect of cholecalciferol (100,000 UI once per week or placebo) for 3 months, in patients on chronic dialysis, who had nutritional vitamin D deficiency (25(OH)D3 ≤20ng/mL). The 25(OH)D3 detection was performed by quimioluminescence; and we use Flow cytometry to evaluate IL6, IFN‐y, TLR7, TLR9, VDR, CYP27 and CYP24 expression on lymphocytes B and T, at baseline and after 3 months. Results: Cholecalciferol increased 25(OH)D3 levels (16,00±4,44 vs 42,81±13,06, p=0,01) and reduced PTH levels (525,3 (128‐1775) vs 484,8 (86‐2264, p=0,03), but have no impact on calcium, phosphorus or FGF23 levels. Additionally, we observed a reduced expression of TLR7 (305±78 vs 252±45, p=0,01), TLR9 (1864±700 vs 1084 ±370, p=0,001 and CYP24 (284±136 vs 200±86, p=0,01), and increased of VDR (730 ±360 vs 965±440, p=0.006) and CYP27 (245±38 vs 442±380, p=0.04) expression. No changes were observed in placebo group. Conclusions: Cholecalciferol treatment in dialysis patients showed to be safe and efficient to correct hipovitaminosis D. In addition, we observed impact of 25(OH)D3 repletion on reduction of expression of the TLR7, TLR9, IFN‐y and improve of regulatory mechanisms associated with intracellular production of vitamin D on lymphocytes from CDK patients. These results suggests that cholecalciferol treatment play an important role on TLRs expression as an anti‐inflammatory and that this may contributed to a better systemic inflammation response in CKD patients.