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比较鼻内耐受和口服耐受对预防胶原诱导的小鼠关节炎的作用。

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

作者信息

Higuchi K, Kweon M N, Fujihashi K, McGhee J R, Kiyono H

机构信息

Department of Microbiology, The Immunobiology Vaccine Center, University of Alabama at Birmingham, USA.

出版信息

J Rheumatol. 2000 Apr;27(4):1038-44.

PMID:10782834
Abstract

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.

摘要

目的

据报道,口服或经鼻给予牛II型胶原蛋白(CII)或其肽可抑制小鼠和大鼠胶原诱导性关节炎(CIA)的发展。我们研究了每种给药途径给予的CII对DBA/1J小鼠CIA的抑制作用,以确定哪种途径更具优势。

方法

雄性小鼠在弗氏完全佐剂中注射两次CII以诱导CIA。在诱导CIA之前,经鼻给予1、10或40微克CII,共15次;口服给予10、100、500或1000微克CII,共10次。检测关节炎的发展、关节炎评分、CII特异性迟发型超敏反应(DTH)以及CII特异性抗体水平。

结果

经鼻给予10微克CII,共15次,具有最显著的抑制作用,疾病发生率降低50%,并抑制CII特异性IgG抗体和DTH反应。在所有口服给药的小鼠中,接受500微克CII,共10次的小鼠显示出最大的抑制潜力。然而,该治疗仅使疾病发作延迟约3周,降低了CII特异性IgG抗体水平,但未能抑制DTH反应。

结论

与口服给药相比,经鼻给予CII能更大程度地减少CIA的发展,并抑制CII特异性T细胞和抗体反应。

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