title: Therapeutic effects of TACI-Ig on rats with adjuvant-induced arthritis via attenuating inflammatory responses.
abstract: OBJECTIVE
  To investigate the effects of TACI-Ig, a recombinant fusion protein that modulates B- and T-cell activation by binding and neutralizing B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), in an established adjuvant-induced arthritis (AA) rat model.
  
  
  METHODS
  Rats with experimental arthritis were randomly separated into different groups and then treated with TACI-Ig (0.7, 2.1, 6.3 mg/kg), rhTNFR-Fc (2.8 mg/kg), MTX (0.5 mg/kg) or IgG-Fc (6.3 mg/kg), from Day 16 to Day 34 after immunization. Arthritis was evaluated by hind paw swelling, polyarthritis index and histopathological examination. Activities of BLyS, APRIL, IL-1β, IL-2, IL-10, TGF-β1, PGE(2), TNF-α, IFN-γ, immunoglobulin (Ig)G1, IgG2a, IgM and IgA were assessed by ELISA. Cluster of differentiation (CD)20 expression was detected by immunohistochemical analysis.
  
  
  RESULTS
  TACI-Ig (2.1, 6.3 mg/kg) treatment significantly reduced the severity of established arthritis using the methods of clinical observation and histopathological examination. TACI-Ig treatment inhibited expression of IgM, decreased the expression of BLyS and APRIL and regulated the balance of pro-inflammatory and anti-inflammatory cytokines in serum of AA rats. Immunohistochemical analysis demonstrated that CD20 production was reduced in spleen.
  
  
  CONCLUSIONS
  Data presented here demonstrate that administration of TACI-Ig significantly attenuates progression of experimental arthritis, with reductions in inflammatory response and bone and joint destruction.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China, Hefei 230032, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.forename: Yujing
authors.initials: Y
authors.lastname: Wu
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Qiong
authors.initials: Q
authors.lastname: Qin
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Xie
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.forename: Shangxue
authors.initials: S
authors.lastname: Yan
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.forename: Qingtong
authors.initials: Q
authors.lastname: Wang
authors.forename: Huaxun
authors.initials: H
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.forename: Wuyi
authors.initials: W
authors.lastname: Sun
authors.forename: Juan
authors.initials: J
authors.lastname: Jin
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D053264:B-Cell Activating Factor / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005620:Freund's Adjuvant / Q000009:adverse effects; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D007596:Joints / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D011993:Recombinant Fusion Proteins; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D005620:Freund's Adjuvant; C524618:TACI receptor-IgG Fc fragment fusion protein