EFFECTS OF FK506, 15-DEOXYSPERGUALIN, AND CYCLOSPORINE ON EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IN THE RAT

被引：27

作者：

MOCHIZUKI, M

KAWASHIMA, H

机构：

[1] Department of Ophthalmology, Kurume University School of Medicine

[2] Department of Ophthalmology, Tokyo University Branch Hospital

来源：

AUTOIMMUNITY | 1990年 / 8卷 / 01期

关键词：

FK506; 15-DEOXYSPERGUALIN; CYCLOSPORINE; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; RETINAL S-ANTIGEN; RATS;

D O I：

10.3109/08916939008998430

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The effects of two novel immunosuppressants, FK506 and 15-deoxyspergualin (15-DSG), on experimental autoimmune uveoretinitis (EAU) were evaluated in the rat. Rats were immunized with retinal soluble antigen (S-antigen) and treated with FK506 or 15-DSG, and the disease induction as well as the immune responses to the antigen were examined. The results were compared with animals treated with cyclosporine (CsA) which has been widely used to treat refractory uveitis in humans. A dose-response study showed that FK506 suppressed EAU induction at doses 10-30 times lower than CsA when given on days 0-14 postimmunization, while 15-DSG suppressed the disease development at doses very similar to CsA. As with CsA, FK506 suppressed EAU induction when given only in the induction phase (days 0-5 postimmunization) or in the effector phase (days 7-12), but at doses much lower than CsA. On the other hand, 15-DSG suppressed EAU only at toxic doses with these schedules. The antigen specific mitotic response of lymphocytes was markedly suppressed by the three agents, while the antigen specific antibodies in sera were suppressed by 15-DSG and FK506 but not by CsA at doses effective in suppressing the disease induction. More significant findings were uniquely prolonged immunosuppressive effects of FK506: EAU induction as well as the immune responses to S-antigen were suppressed long after the cessation of drug treatment. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

引用

页码：37 / 41

页数：5

共 23 条

[1] Nussenblatt R.B., Palestine A.G., Uveitis. Fundamentals and Clinical Practice, (1989)
[2] Hess A., Tutsckka P.J., Santos G.W., Effect of cyclosporine on the interaction of cytotoxic T lymphocytes: Role of interleukin 1 and interleukin 2, Cyclosporine, pp. 32-42, (1984)
[3] Hess A., Esa A.H., Colombani P.M., Mechanisms of actions of cyclosporine: Effects on cells of the immune system and on subcellular events in T cell activation, Cyclosporine. Nature of the Agent and its Immunologic Actions, pp. 29-40, (1988)
[4] Nussenblatt R.B., Palestine A.G., Chan C.C., Mochizuki M., Yancy K., Effectiveness of cyclosporine therapy for Behcet's disease, Arth Reum, 28, pp. 671-679, (1985)
[5] Masuda K., Nakajima A., Urayama A., Nakae K., Kogure M., Inaba G., Double masked trial of cyclosporine versus colchicine and long-term open study of cyclosporine in Behcet's disease, Lancet, 1, pp. 1093-1096, (1989)
[6] Kino T., Hatanabe H., Hashimoto M., Nishiyama M., Goto T., Okuhara M., Kohsaka M., Aoki H., Imanaka H., FK506, a novel immunosuppressant isolated from a streptomyces: I. Fermentation, isolation, and physio-chemical and biological characteristics, J. Antibiotics, 40, pp. 1249-1255, (1987)
[7] Kino T., Hatanaka H., Miyato S., Inamura N., Nishiyama M., Yajima T., Goto T., Okuhara M., Kohsaka M., Aoki H., Ochiai T., FK506, a novel immunosuppressant isolated from a streptomyces: II. Immunosuppressive effect of FK50, In Vitro-J Antibiotics, 40, pp. 1256-1265, (1987)
[8] Iwasawa H., Kondo S., Ikeda D., Takeuchi T., Umezawa H., Synthesis of (-)-15-Deoxyspergua Iin and (-)-Spergualin-15-phosphate, J. Antibiotics, 35, pp. 1665-1669, (1982)
[9] Sawada S., Suzuki G., Kawase Y., Takaku F., Novel im-munosuppresive agent, FK506: Invitro effects on the cloned T cell activation, J. Immunol, 139, pp. 1797-1803, (1987)
[10] Sakuma S., Kosazka H., Kiyotaki C., Fujitsu T., Senoh H., Hamaoka T., Fujiwara H., Mechanism of the inhibition of T cell activation by immunosuppressant FK506, Abstracts of Workshop Presentation of The 4th International Conference on Immunopharmacology., (1988)

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