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Therapeutic effects of adiponectin-mediated trimeric sTNFRII on collagen-induced arthritis

Jimin Gao1*, Mansheng Luo2 and Zhiming Hu3
  • 1 Wenzhou Medical College, China
  • 2 Jinggangshan University, China
  • 3 Southern Medical University, China

We have developed a novel trimeric sTNFRII, named sTNFRII-gAD fusion protein, which exhibits a higher in vitro antagonistic efficacy for TNFα compared with sTNFRII-Fc. This study was aimed to investigate the anti-arthritic capacity of sTNFRII-gAD in a rat collage-induced arthritis model (CIA). The rats were injected intradermally with 200μg collagen type II (CII) at day 0 and day 7. Three days post the second CII injection (day 10), the rats were intraperitoneally given 200μg of sTNFRII-gAD or sTNFRII-Fc, or sterile saline. Effects of sTNFRII-gAD treatment were evaluated by CIA incidence, severity and pathological changes. Serum TNFα, IL-17A and regulatory T cell (Treg) in periphery were examined at day 10 and 16, respectively. Our results showed that sTNFRIIgAD significantly decreased CIA incidence and severity (p<0.05), and that sTNFRII-gAD treatment led to a dramatic reduction in cartilage and bone damage. Moreover, the increase in serum anti-CII and IL-17A, and the reduction in Treg population were suppressed (p<0.05) by the administration of sTNFRII-gAD or sTNFRII-Fc. TNFα was found to be accumulated in serum in the groups treated with sTNFRII-gAD or sTNFRII-Fc compared with the group treated with saline (p<0.05). Noteworthily, sTNFRII-gAD showed a better efficacy than sTNFRII-Fc in CIA incidence, pathological changes in cartilage and the elevation of anti-CII antibody, indicating that sTNFRII-gAD is potentially a more efficacious TNFα antagonist for rheumatoid arthritis.

Acknowledgements

The work was supported in part by the following grants: National Major Specific Project for Innovation of New Pharmaceuticals (2009ZX09103-649), Key Science and Technology Innovation Team of Zhejiang Province, Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents, Research & Development Foundation of Ministry of Health (No. 201231029), Development Foundation of Zhejiang Provincial Department of Education (No. Y201016518), Wenzhou Municipal Research Program (G20090142 and Y20100274), and Guangdong Provincial Project for R & D in Industrialization Technology (2010B031200004).

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Keywords: TNFα antagonist, soluble TNFRII, Adiponectin, fusion protein, collage-induced arthritis

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Translational immunology and immune intervention

Citation: Gao J, Luo M and Hu Z (2013). Therapeutic effects of adiponectin-mediated trimeric sTNFRII on collagen-induced arthritis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01125

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Received: 20 Jul 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Jimin Gao, Wenzhou Medical College, Wenzhou, China, jimingao64@163.com