Transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig) is

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). 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 IFN-alphaJ IgG1 IgG2a and IgM in AA rat spleen were measured by enzyme-linked immunosorbent assay. Administration of TACI-Ig significantly reduced the COG 133 arthritis global assessment and SJC decreased spleen index and ameliorated histopathological manifestations of rat AA. Suppressing the levels COG 133 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 COG 133 in spleen. < 0·05 were considered significant. Results Effects of TACI-Ig on arthritis global assessment CFA injection was administered on day 0 and the secondary inflammatory reaction occurred on days 14-15. Treatment with TACI-Ig (6·3 mg/kg) and rhTNFR : Fc (2·8 mg/kg) diminished arthritis global assessment significantly in AA rats from days 30 to 34 (< 0·05) (Fig. 1). Fig. 1 Effects of transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig) on arthritis global assessment. TACI-Ig (6·3 mg/kg) diminished significantly arthritis global assessment from days 30 to 34 (... Effects of TACI-Ig on SJC After immunization SJC increased in the AA model group and IgG-Fc group compared with the normal group. Treatment with TACI-Ig (6·3 mg/kg) diminished SJC significantly in AA rats from days 30 to 34 (< 0·05) and rhTNFR : Fc (2·8 mg/kg) diminished parameters significantly from days 26 to 34 (< 0·05) (Fig. 2). Fig. 2 Effects of transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig) on swollen joint count (SJC). TACI-Ig (6·3 mg/kg) diminished SJC significantly from day 30 to day 34 (< 0·05). ... Effects of TACI-Ig on histopathology In COG 133 the AA model group and IgG-Fc treatment group immune response resulted in increased cellularity and size in the follicles and marginal zone and the appearance of prominent GC in white pulp. Administration of TACI-Ig (0·7 2 and 6·3 mg/kg) and rhTNFR : COG 133 Fc (2·8 mg/kg) alleviated these abnormalities in varying degrees (Fig. 3). Fig. 3 Effects of transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig) on histopathology of spleen (haematoxylin and eosin ×100). In the adjuvant arthritis (AA) model and IgG-Fc groups immune response ... In the normal rat ankle joint synoviocytes were monolayered and there was no infiltration of inflammatory cells. In the AA model group and IgG-Fc treatment group synoviocytes proliferated over three to eight layers with pannus formation and articular cartilage was eroded and infiltrated with inflammatory cells. These abnormalities were alleviated significantly in AA rats after administration of TACI-Ig (0·7 2 and 6·3 mg/kg) and rhTNFR : Fc (2·8 mg/kg) (Fig. 4). Fig. 4 Effects of transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig) on histopathology of joint (haematoxylin and eosin × 100). Joints of the adjuvant arthritis (AA) model and IgG-Fc groups with ... Effects of TACI-Ig on spleen index and thymus index The spleen index and thymus index of the AA model group and IgG-Fc group increased significantly when compared to the normal group (< 0·01). After administration of TACI-Ig (2·1 and 6·3 mg/kg) the spleen index decreased significantly compared to the model group (< 0·01). Administration of TACI-Ig (0·7 2 and 6·3 mg/kg) COG 133 and rhTNFR : Fc (2·8 mg/kg) had no significant influence on the thymus index in AA rats (Table 1). Table 1 Effects of transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig) on spleen index and thymus index. Effects of TACI-Ig on production of cytokine and Ig in spleen Figures 5 and ?and6 6 respectively showed the effects of TACI-Ig on BLyS IL-17 IFN-γ IgG1 IgG2a and IgM levels in AA rat spleen. BLyS IL-17 IFN-γ IgG1 IgG2a and IgM levels in the AA modeland IgG-Fc treatment group were significantly higher when compared to the normal group (< 0·01). Administration of TACI-Ig (0·7 2 and 6·3 mg/kg) and rhTNFR : Fc (2·8 mg/kg) decreased BLyS IL-17 IFN-γ IgG1 IgG2a and IgM levels in varying.