[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 microg/dose, daily for 5 doses and continuing every other day for other 7 doses). Wild CII263-272 peptide (100 microg/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-gamma 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-beta mRNA.


RESULTS
(1) Following treatment with the altered CII263-272 peptide, arthritis 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, P<0.05). The serum IFN-gamma 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 (P<0.05). 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-beta mRNA.


CONCLUSIONS
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-gamma, and inhibit Th1 response in vivo. Altered C II263-272 peptide may be therapeutic for RA.
Zhao
Jin Xia
JX
Department of Rheumatology & Immunology, Peking University People's Hospital, Beijing, China.
Li
Ru
R
He
Jing
J
Shi
Jin Xia
JX
Li
Zhan Guo
ZG
D000281:Administration, Intranasal; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D003094:Collagen / Q000008:administration & dosage* / Q000737:chemistry; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology
D007074:Immunoglobulin G; D010446:Peptide Fragments; C540887:collagen II (263-272), Ala(267,270,271)-; D007371:Interferon-gamma; D003094:Collagen