Induction of immunologic tolerance to collagen induced arthritis mice by oral administration of chicken type Ⅱ collagen / 北京大学学报(医学版)

ABSTRACT

Objective: To assess the immunological effects by orally administering chicken type Ⅱ collagen(CCⅡ) on collagen-induced arthritis(CIA)mice. To assess the effect on producing IL-1 of peritoneal macrophage in adjuvant arthritis rats by orally administering CCⅡ. Methods: Arthritis were induced in Kunming mice by immunization with chicken type Ⅱ collagen with Freund's complete adjuvant, followed by an interperitoneal injection of CCⅡ 3 weeks later.Chicken type Ⅱ collagen was orally administered from 5 days prior to the induction of arthritis to 14 days after inducing arthritis model. The animals were examined visually twice weekly for polyarthritic signs of swollen and erythemic limbs. Quantitation of antibody level of CIA mice was measured by ELISA method. Subpopulations of T lymphocytes in mice were evaluated by flow cytometry method. IL-1 assay was evaluated by ELISA method. Results: Joint swelling was significantly reduced at a dose of 5 μg.kg-1 and 50 μg.kg-1 of CCⅡ, but not at 250 μg.kg-1. The level of anti-collagen antibodies was also reduced at a dose of 5 μg.kg-1 and 50μg.kg-1 (OD value from CIA model control 0.242±0.073 to CCⅡ 5 μg.kg-1 0.123±0.029 and CCⅡ 50 μg.kg-1 0.110±0.075 respectively). Subpopulations of T-lymphocytes were changed by orally administering of CCⅡ, and the ratio of L3T4+/Lyt-2+ was lowered (the ratio from 1.71 of CIA model control to 1.21, 1.51 of administered CⅡ 5 μg.kg-1, 50μg.kg-1 respectively.) after administering CCⅡ. IL-1 level can be reduced (the value from adjuvant arthritis model control 62.8±0.9 to 43.4±1.3, 49.7±0 ng.L-1 administered CⅡ 5 μg.kg-1, 50μg.kg-1 respectively). Conclusion: Arthritis sign in CIA animal model can be suppressed by oral CCⅡ. The effects may be involved by influencing the mechanisms both humoral and cellular immunity. The effects occurred at lower doses of CCⅡ. These results demonstrated the biologic relevance of by-stander suppression associated with oral tolerance, and the potential use of this approach to treat human inflammatory joint diseases.