Therapeutic effects of TACI-Ig on rat with adjuvant arthritis.

Abstract

Transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig) is a human fusion protein that binds and neutralizes both B lymphocyte stimulator (BLyS), a cytokine shown to be a key regulator of B cell maturation, proliferation and survival, and a proliferation-inducing ligand (APRIL). Rat adjuvant arthritis (AA) is an experimental animal model of rheumatoid arthritis (RA), which is mainly dependent on T cells and neutrophil-mediated cytokine production. The purpose of the present study was to investigate the effects of TACI-Ig on rat AA. Rat AA was induced by intradermal injection of 0·1 ml complete Freund's adjuvant (CFA). TACI-Ig (0·7, 2·1 and 6·3 mg/kg), recombinant human tumour necrosis factor-α receptor (rhTNFR) : Fc (2·8 mg/kg) and IgG-Fc (6·3 mg/kg) were administered subcutaneously every other day from days 16 to 34 after immunization. Arthritis was evaluated by arthritis global assessment and swollen joint count (SJC). The ankle joint and spleen were harvested for histopathological examination. Spleen index and thymus index were calculated. The levels of BLyS, interleukin (IL)-17, interferon (IFN)-γ, IgG1, IgG2a and IgM in AA rat spleen were measured by enzyme-linked immunosorbent assay. Administration of TACI-Ig significantly reduced the arthritis global assessment and SJC, decreased spleen index and ameliorated histopathological manifestations of rat AA. Suppressing the levels of BLyS, IL-17, IFN-γ and Ig in AA rat spleen were observed after administration of TACI-Ig. These results showed that TACI-Ig significantly inhibited the degree of rat AA, and the inhibitory effects might be associated with its ability to reduce BLyS, proinflammatory cytokines and Ig levels in spleen.

• Authors: D Wang, Y Chang, Y Wu, L Zhang, S Yan, G Xie, Q Qin, J Jin, W Wang, J Fang, W Wei
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 163 Issue 2 Pg. 225-34 (Feb 2011) ISSN: 1365-2249 [Electronic] England
• PMID: 21155990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.

Chemical References

• Adjuvants, Immunologic
• B-Cell Activating Factor
• Immunoglobulin G
• Immunoglobulin M
• Interleukin-17
• Receptors, Tumor Necrosis Factor
• Recombinant Fusion Proteins
• Interferon-gamma
• TACI receptor-IgG Fc fragment fusion protein

Topics

• Adjuvants, Immunologic (adverse effects)
• Animals
• Ankle Joint (immunology, pathology)
• Arthritis, Experimental (drug therapy)
• B-Cell Activating Factor (analysis, immunology)
• Immunoglobulin G (immunology)
• Immunoglobulin M (analysis, immunology)
• Interferon-gamma (analysis, immunology)
• Interleukin-17 (analysis, immunology)
• Male
• Rats
• Rats, Sprague-Dawley
• Receptors, Tumor Necrosis Factor (immunology)
• Recombinant Fusion Proteins (therapeutic use)
• Spleen (immunology, pathology)