title: 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.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Hefei RC Biotechnologies Ltd, Yantai, China.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Chang
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Yan
authors.forename: G
authors.initials: G
authors.lastname: Xie
authors.forename: Q
authors.initials: Q
authors.lastname: Qin
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Fang
authors.forename: W
authors.initials: W
authors.lastname: Wei
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000818:Animals; D000843:Ankle Joint / Q000276:immunology / Q000473:pathology; D001169:Arthritis, Experimental / Q000188:drug therapy*; D053264:B-Cell Activating Factor / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D020381:Interleukin-17 / Q000032:analysis / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020381:Interleukin-17; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; C524618:TACI receptor-IgG Fc fragment fusion protein