Therapeutic Effects of TACI-Ig on Rats With Adjuvant-Induced Arthritis via Attenuating Inflammatory Responses

Rheumatology (Oxford). 2011 May;50(5):862-70. doi: 10.1093/rheumatology/keq404. Epub 2010 Dec 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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