Hepatorenal pathologies in TNF-transgenic mouse model of rheumatoid arthritis are alleviated by anti-TNF treatment

Abstract

Objective To examine and quantify liver and kidney lesions and their response to anti-TNF therapy in TNF-Tg mouse model of rheumatoid arthritis. Methods Female TNF-Tg (Tg3647) mice were used as the animal model of chronic rheumatoid arthritis. Ultrasound, immunofluorescence and histology staining, serology test and real-time PCR were used to examine the pathological changes in liver and kidney. Results TNF-Tg mice showed a significant decrease in body weight and a dramatic increase in the volumes of gallbladder, knee cavity, and popliteal lymph nodes. Liver and kidney of TNF-Tg mice were demonstrated increased chronic inflammation, accumulation of immune cells, fibrosis and senescence, compared to the wide-type (WT) mice. Moreover, up-regulation of inflammatory factors and impaired normal function were also observed in the liver and kidney of TNF-Tg mice. The inflammation infiltration, fibrosis and senescence in liver and kidney of female TNF-Tg mice were improved after anti-TNF treatment, and better treatment effects were achieved at 8 weeks of intervention. Conclusions We found that TNF drives the development of liver and kidney pathology in female TNF-Tg mice, and there are limitations in the loss of utility of Anti-TNF for prolonged treatment of RA-associated hepatic and renal injury. This study provided a reliable and high clinically relevant animal model for the further study to explore the molecular mechanisms and drug discovery of hepatorenal pathologies in RA.