title: Preventive Effect of a Novel Recombinant sTNFRII on Collagen-Induced Arthritis.
abstract: We developed a novel trimeric sTNFRII fusion protein, named sTNFRII-gAD, which exhibited a higher in vitro antagonistic efficacy for TNFα in comparison with sTNFRII-Fc. This study aimed to investigate the arthritic protection of sTNFRII-gAD in a rat collagen-induced arthritis (CIA). The rats were injected intradermally with collagen type II at days 0 and 7. Three days after the second injection (day 10), the rats were intraperitoneally given sTNFRII-gAD or sTNFRII-Fc, or PBS. Effects of treatments were examined with respect of CIA incidence, severity and pathological changes. Serum TNFα, IL-17A and regulatory T cell (Treg) in periphery were determined at days 10 and 16, respectively. Our results showed that sTNFRIIgAD significantly reduced CIA incidence and severity (p < 0.05); meanwhile it led to a dramatic improvement in cartilage and bone damage. Moreover, the increase in serum anti-CII and IL-17A, and the reduction in Treg population were inhibited (p < 0.05) by sTNFRII-gAD or sTNFRII-Fc. Serum TNFα was found to be accumulated in the groups treated with sTNFRII-gAD or sTNFRII-Fc compared with the group treated with PBS (p < 0.05). It is noteworthy that sTNFRII-gAD displayed 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 anti-TNFα agent for rheumatoid arthritis.
authors.affiliation: Department of Microbiology & Immunology, JingGangShan University , Jian, Jiangxi , China .
authors.forename: Mansheng
authors.initials: M
authors.lastname: Luo
authors.forename: Ai
authors.initials: A
authors.lastname: Zhao
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Lingxia
authors.initials: L
authors.lastname: He
authors.forename: Yuntin
authors.initials: Y
authors.lastname: Guo
authors.forename: Dandan
authors.initials: D
authors.lastname: Tian
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Hu
authors.forename: Jimin
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D005260:Female; D007274:Injections, Intraperitoneal; D020381:Interleukin-17 / Q000097:blood; D007719:Knee Joint / Q000473:pathology; D018655:Lymphocyte Count; D051381:Rats; D017208:Rats, Wistar; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000627:therapeutic use; D012995:Solubility; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000906:Antibodies; D024043:Collagen Type II; D020381:Interleukin-17; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: Collagen-induced arthritis; TNFα; gAD; soluble TNFRII