Effects and mechanisms of vitamin A and vitamin E on the levels of serum leptin and other related cytokines in rats with rheumatoid arthritis

Abstract

Leptin has been identified as an important cytokine in the inflammatory networks of rheumatoid arthritis (RA). Higher serum leptin levels may accelerate the development of RA. This study aimed to examine the effects of vitamin A (VitA) and vitamin E (VitE) on the levels of leptin and other related experimental and clinical indices, and to explore the mechanisms of these effects through the Janus kinase/signal transducer and activator of transcription (STAT) signal transduction pathway in rats with collagen-induced arthritis (CIA). CIA model rats were established by the intradermal injection of bovine type II collagen emulsified in incomplete Freund’s adjuvant, followed by a booster intradermal injection. Four weeks later, the CIA model rats were treated with 42.86 μg retinol equivalents/kg body weight (b.w.) VitA or 200 mg/kg b.w. VitE for four weeks. The levels of leptin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, IL-4, C-reactive protein (CRP) and rheumatic factor were measured by ELISA using commercial kits, and the erythrocyte sedimentation rate (ESR) was determined. In addition, the expression levels of phosphorylated (p)-STAT1, p-STAT3 and leptin in the synovium were evaluated by western blot analysis. The results indicated that VitA and VitE significantly reduced the levels of leptin, TNF-α, IL-6 and CRP and the ESR and significantly increased the levels of IL-10 compared with those of the model group. Furthermore, significantly reduced p-STAT3 protein expression levels were observed in the VitA and VitE groups. In conclusion, VitA and VitE reduced the levels of serum leptin protein and other cytokines. Furthermore, VitA and VitE also reduced the p-STAT3 protein levels. The present study may provide a novel approach for the treatment of RA.