Mucosal administration of altered CII263-272 peptide inhibits collagen-induced arthritis

Objective:To evaluate the effect of mucosal administration of altered collagen Ⅱ(CⅡ)263-272 peptide(267Q→A,270K→A and 271G→A) on collagen induced arthritis(CIA),and to explore the mechanism of the inhibitory effect of the altered CⅡ263-272 peptide on CIA.Methods:CIA was induced in Lewis rats by immunization with bovine CⅡ.Altered CⅡ263-272 peptide was given intranasally beginning from the onset of arthritis(100 μg/dose,daily for 5 doses and continuing every other day for other 7 doses).Wild CⅡ263-272 peptide(100 μg/dose) or PBS was administered as controls with the same procedure.Therapeutic effects were evaluated by arthritis scores,body weight change,and joint pathologic scores.The anti-CⅡ antibody and its subtypes were measured with ELISA.The cytokines of IFN-γ and IL-10 were measured with ELISA.The induction of regulatory T cells was assessed by FACS analysis of percentage of peripheral CD4+CD25+ T cells,and by real-time PCR analysis of the expression of Foxp3 and TGF-β mRNA.Results:(1) Following treatment with the altered CⅡ263-272 peptide,arthiritis scores were reduced and body weight was increased.The mean arthritis scores of rats treated with altered peptide,wild peptide and PBS were 2.50±2.43,4.50±2.23 and 6.33±2.73,respectively.The altered peptide could retard the histologic lesion of the joints.(2) The titers of anti-CⅡ antibodies IgG and IgG1 in the three groups were similar,but the IgG2a in altered peptide-treated rats decreased markedly as compared with PBS-treated rats(0.56±0.19 vs 0.95±0.29,P0.05).The serum IFN-γ in rats treated with altered peptide,wild peptide and PBS were(185.33±29.77),(231.62±41.82) and(220.64±83.61) ng/L,respectively(P0.05).No difference was found in the levels of serum IL-10 among the three groups.(3) There was no significant difference in the percentage of peripheral CD4+CD25+ T cells and the expression level of Foxp3 and TGF-β mRNA.Conclusion:Mucosal administration of altered CⅡ263-272 peptide could effectively inhibit the progression of CIA.It can decrease the IgG2a subtype of anti-CⅡ antibodies and IFN-γ,and inhibit Th1 response in vivo.Altered CⅡ263-272 peptide may be therapeutic for RA.