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: 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
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 50 Issue 5 Pg. 862-70 (May 2011) ISSN: 1462-0332 [Electronic] England
• PMID: 21186171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B-Cell Activating Factor
• Recombinant Fusion Proteins
• Tumor Necrosis Factor Ligand Superfamily Member 13
• Freund's Adjuvant
• TACI receptor-IgG Fc fragment fusion protein

Topics

• Animals
• Arthritis, Experimental (drug therapy, metabolism, physiopathology)
• B-Cell Activating Factor (metabolism)
• Bone and Bones (drug effects, pathology)
• Disease Models, Animal
• Disease Progression
• Freund's Adjuvant (adverse effects)
• Inflammation (metabolism, physiopathology, prevention & control)
• Joints (metabolism, physiopathology)
• Male
• Rats
• Rats, Sprague-Dawley
• Recombinant Fusion Proteins (pharmacology, therapeutic use)
• Spleen (drug effects, pathology)
• Treatment Outcome
• Tumor Necrosis Factor Ligand Superfamily Member 13 (metabolism)