Objective: To determine whether low-dose TGF-β1 and/or IL-6-receptorα monoclonal antibody (anti-IL-6Rα) can be used to delay renal damage and preserve renal function by rebalancing regulatory T (Treg)/Th17 cells during the course of early diabetic nephropathy (DN) induced by streptozotocin (STZ).
Methods: Diabetes was induced in C57BL/6 mice by multiple STZ injection. Low-dose TGF-β1 (0.1 μg/mouse/week) and/or anti-IL-6Rα (10 μg/mouse/week) were administered 6 dozes after STZ injection. After 40 days of diabetes onset, metabolic indices, renal structure, activated Akt and Stat3, Treg/Th17 balance, markers and inflammatory cytokines, and oxidative stress in glomeruli were assessed.
Results: Low-dose TGF-β1, instead of causing renal damage, decreased blood glucose, ameliorated kidney hypertrophy, attenuated oxidative stress, maintained activated Stat3, and induced Treg/Th17 balance in early DN. Interestingly, low-dose TGF-β1+anti-IL-6Rα or anti-IL-6Rα alone did not attenuate DN.
Conclusions: This study provides convincing experimental evidence of the protective effects of low-dose TGF-β1 in improving metabolic disorder and slowing renal damage in early DN.
Keywords: Diabetic nephropathy; IL-6 blockade; Regulatory T cells; Streptozotocin; TGF-β1; Th17 cells.
© 2013.