Therapeutic effects of TACI-Ig on rats with adjuvant-induced arthritis via attenuating inflammatory responses

Yan Chang, Yujing Wu, Di Wang, Wei Wei, Qiong Qin, Guoxiong Xie, Lingling Zhang, Shangxue Yan, Jingyu Chen, Qingtong Wang, Huaxun Wu, Feng Xiao, Wuyi Sun, Juan Jin, Wenxiang Wang

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46 Scopus citations

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.

Original languageEnglish (US)
Article numberkeq404
Pages (from-to)862-870
Number of pages9
JournalRheumatology
Volume50
Issue number5
DOIs
StatePublished - May 1 2011
Externally publishedYes

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Keywords

  • A proliferation-inducing antigen
  • Arthritis
  • Autoimmune
  • B lymphocyte stimulator
  • T cell
  • TACI-Ig

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Chang, Y., Wu, Y., Wang, D., Wei, W., Qin, Q., Xie, G., Zhang, L., Yan, S., Chen, J., Wang, Q., Wu, H., Xiao, F., Sun, W., Jin, J., & Wang, W. (2011). Therapeutic effects of TACI-Ig on rats with adjuvant-induced arthritis via attenuating inflammatory responses. Rheumatology, 50(5), 862-870. [keq404]. https://doi.org/10.1093/rheumatology/keq404