口服鸡源性Ⅱ型胶原蛋白诱导实验性CIA小鼠免疫耐受(英文)

Induction of immunologic tolerance to collagen induced arthritis mice by oral administration of chicken type Ⅱ collagen

评价口服鸡源性Ⅱ型胶原蛋白 (chickentypeⅡcollagen ,CCⅡ )对胶原性关节炎 (collagen inducedarthritis,CIA)小鼠的抗炎及免疫作用的影响。方法 :以CCⅡ蛋白与福氏完全佐剂免疫昆明种小鼠 ,并于第 2 1天强化免疫 1次。CCⅡ于致敏前第 5天即开始灌胃给药 ,共 2 0d。每周两次评价多发性关节炎评分。以ELISA法测定CIA小鼠血清抗CⅡ抗体。以流式细胞测定法测定小鼠脾T淋巴细胞亚型。以ELISA法测定佐剂性关节炎大鼠腹腔巨噬细胞IL 1分泌水平。结果 :口服CCⅡ 5 μg·kg-1和 5 0 μg·kg-1可明显降低多发性关节炎评分值 ,而25 0 μg·kg-1剂量组则无作用 ;CCⅡ 5 μg·kg-1剂量组可抑制CIA小鼠升高了的血清抗CⅡ抗体水平 ;口服CCⅡ可使CIA小鼠升高的L3T4+/Lyt 2 +值有所降低。口服CCⅡ可使佐剂性关节炎大鼠升高了的IL 1水平有所降低。结论 :口服CCⅡ可抑制CIA小鼠多发性关节炎的发生 ,此作用可能有体液免疫和细胞免疫两种机制参与。以上作用的发生为剂量依赖性的 ,即小剂量作用最强。

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 50 μg·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 , 50 μg·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 , 50 μg·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.