title: BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats.
abstract: OBJECTIVE
  To investigate the therapeutic effects of BF02 on adjuvant arthritis (AA) in rats and the regulatory effects of BF02 on T lymphocyte function.
  
  
  METHODS
  SD rats received a single intradermal injection of Freund's complete adjuvant emulsion into the right hind metatarsal footpad. After the onset of AA, the rats were injected BF02 (1, 3, or 9 mg/kg, sc) every 3 d for a total of 15 d. Intragastric administration of methotrexate (MTX, 0.5 mg/kg, every 3 d for a total of 15 d) was taken as the positive control drug. Arthritis index, swollen joint count, ankle joint histopathology, spleen histopathology and the paw radiography were used for evaluating the drug effects on AA rats. T lymphocyte function was assessed by measuring T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression levels, and percentage of T lymphocyte subsets.
  
  
  RESULTS
  In the AA rats, remarkable secondary inflammatory responses exhibited, accompanied by significantly higher levels of IL-1, IL-6, TNF-α, IL-17, LTα, RANKL, and MMP-13. The expression of IL17 and TNF-α mRNAs was also substantially higher than in normal rats. The percentages of CD3(+)CD4(+) and CD4(+)CD25(+) T lymphocytes were increased, whereas the percentages of CD4(+)CD62L(+) and CD4(+)CD25(+)FoxP3(+) T lymphocytes were decreased. Treatment of the AA rats with BF02 (9 mg/kg) or MTX significantly decreased the arthritis index, swollen joint count and arthritis global assessment. Moreover, both BF02 (9 mg/kg) and MTX significantly inhibited T lymphocyte proliferation, and blocked the above mentioned aberrance in T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression, and percentages of T lymphocyte subsets.
  
  
  CONCLUSIONS
  BF02 exerts therapeutic effects on AA rats via the regulation of T lymphocytes.
authors: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China, Hefei 230032, China.
authors: Shan-shan
authors: SS
authors: Song
authors: Bei
authors: B
authors: Huang
authors: Qing-tong
authors: QT
authors: Wang
authors: Yu-jing
authors: YJ
authors: Wu
authors: Jing-jing
authors: JJ
authors: Fu
authors: Yun-fang
authors: YF
authors: Zhang
authors: Yan
authors: Y
authors: Chang
authors: Jing-yu
authors: JY
authors: Chen
authors: Hua-xun
authors: HX
authors: Wu
authors: Di
authors: D
authors: Wang
authors: Ling-ling
authors: LL
authors: Zhang
authors: Wei
authors: W
authors: Wei
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy; D001175:Arthrography; D049109:Cell Proliferation / Q000187:drug effects; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000008:administration & dosage / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D018501:Antirheumatic Agents; C585239:BF02 protein; D007141:Immunoglobulin Fc Fragments; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins
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