ABSTRACT
Aim To investigate the effect of non-T cell binding peptide(FNS007)on collagen type Ⅱ-induced arthritis(CIA)in mice and the possible mechanisms.Methods The CIA model was induced by intradermal injection of bovine CⅡ+Freunds adjuvant.At the clinical onset of CIA,mice were randomly divided into 6 groups: blank control group(Control),model group,ORENCIA(abatacept)group,FNS007 low dose(1.2 mg·kg-1)group,FNS007 middle dose(2.4 mg·kg-1)group and FNS007 high dose(4.8 mg·kg-1)group.FNS007 was given by intravenous injection on the first day of arthritis and every other day until the study was terminated on d 28 after injection of the drug.The paw thickness and the ankle joint width were measured,and the arthritis scores were recorded.At termination,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and level of anti-CⅡ antibody in serum were examined by enzyme-linked immunosorbent assay(ELISA).Bone injury was analyzed by X-ray imaging,and HE staining was conducted to observe the histopathologic changes and pathological score of ankle tissues.Results CIA models were successfully induced.Compared with CIA group,FNS007 high dose significantly reduced the paw thickness and the ankle joint left-right diameter,lowered arthritis scores in CIA mice,reduced serum concentrations of IFN-γ,IL-6 and anti-CⅡ antibodies,and lowered the radiographic and histologic scores.Compared with CIA group,FNS007 middle dose group showed marked reduction in the arthritis scores,IL-6 content in serum,and inhibion in the radiographic and histologic scores.The arthritis scores,concentration of IFN-γ,the radiographic and histologic scores were significantly reduced in FNS007 low dose group compared with those in model group.Conclusion FNS007 can effectively inhibit the progression of CIA through inhibiting T-cell activation and reducing inflammatory cytokines,anti-CⅡ antibodies,and histoclasia and bone destruction.
ABSTRACT
Objective:To observe the effects of FNS007 on collagen Ⅱ-induced arthritis(CIA) rat models and investigate the underlying mechanism.Methods: CIA model was induced by intradermal injection of Freunds adjuvant and bovine CⅡ.Rats were randomly divided into six groups:normal control group,model group,methotrexate group,high,middle and low doses of FNS007 groups,with 12 rats in each group.FNS007 was gived by intravenous injection,the normal control and model group were administrated with PBS.Observing the paw thickness,ankle joint width and the arthritis scores in the CIA rats during the experiment.On d 22 after injection of the drug, all rats were killed.Interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6 (IL-6) and level of anti-CⅡantibody in serum were examined by enzyme-linked immunosorbent assay (ELISA).The pathological score and radiography of ankle joint were evaluated.Results: Data revealed that FNS007 treated groups showed a significant reduction in paw thickness,ankle joint width and the arthritis scores compared to model group (P<0.05,P<0.01),especially FNS007 high dose goup.The levels of TNF-α,IFN-γ,IL-6 and anti-CⅡantibodies in serum in high dose goup were significantly lower than those of model group(P<0.05,P<0.01).X-ray examination showed that FNS007 could significantly alleviate the damage of joint and decrease the radiographic scores.Pathological examination exhibited that FNS007 could significantly reduce pathological scores,alleviate inflammatory cell infiltration and synovial hyperplasia,improve the histopathological changes.Conclusion: FNS007 has a treating effect on CIA rats,and the mechanisms may be through competitive inhibition of T cell,inhibiting inflammatory cytokines and anti-CⅡantibodies secretion,regulating the abnormal immune responses.