Bystander suppression of murine collagen-induced arthritis by long-term nasal administration of a self type II collagen peptide.

Oral and more recently nasal tolerance have attracted attention as potential treatments of autoimmune disease. Arthritis induced by bovine type II collagen (CII) is a widely used animal model of rheumatoid arthritis, which is here used to investigate the efficacy of nasal treatment by a short peptide. The peptide spans residues 707-721 (designated p707), an epitope of mouse CII that is most strongly recognized after immunization of mice with this self-protein. The treatment was partially effective, but almost only when the peptide was administered in large doses over a prolonged period. Mice immunized with bovine CII respond mainly to other peptides, located in the CB11 fragment around amino acid residues 256-270. The tolerance effect therefore results from intramolecular suppression, between epitopes located in different parts of this large protein.