Comparison of nasal and oral tolerance for the prevention of collagen induced murine arthritis.

OBJECTIVE

Administration of bovine type II collagen (CII) or of its peptide either orally or nasally has been reported to suppress the development of collagen induced arthritis (CIA) in mice and rats. We examined the inhibitory effects of CII delivered by each route on CIA in DBA/1J mice to determine which route was superior.

METHODS

Male mice were injected twice with CII in Freund's complete adjuvant to induce CIA. Before induction of CIA, 1, 10, or 40 microg of CII were administered nasally 15 times and 10, 100, 500, or 1000 microg of CII were given 10 times orally. The development of arthritis, arthritis score, CII-specific delayed-type hypersensitivity (DTH) response, and CII-specific antibody levels were examined.

RESULTS

Nasal administration of 10 microg of CII 15 times had the most prominent suppressive effects, reducing disease incidence by 50% and inhibiting both CII-specific IgG antibody and DTH responses. Of all the mice undergoing oral administration, those receiving 500 microg of CII 10 times showed the greatest suppressive potential. However, the treatment only delayed disease onset for roughly 3 weeks, lowering CII-specific IgG antibody levels but failing to suppress DTH responses.

CONCLUSION

Nasal administration of CII reduced CIA development and inhibited CII-specific T cell and antibody responses to a greater degree than did oral administration.