免疫抑制剂F904的免疫抑制作用

Immunosuppressive activities of immunosuppressant F904

新免疫抑制剂 F90 4是吸水链霉菌 (Streptomyceshygroscopicus) FC90 4产生的三烯大环内酯化合物 ,化学结构研究证实它与新型强效免疫抑制剂西罗莫司 (sirolimus,rapamycin)同质。体外免疫学试验显示F90 4能抑制 PHA诱导的 T淋巴细胞转化 ,抑制作用较环孢素 (Cs A)强约 10 0倍 ,IC5 0 <0 .1nmol/ L;抑制Con A诱导的 T淋巴细胞转化 ,抑制作用同 Cs A相当 ,IC5 0 1～ 10 nmol/ L;F90 4还能抑制 L PS诱导的 Ca2 +不依赖的 B细胞转化 ,IC5 0 1nmol/ L,Cs A的抑制作用则极其微弱。F90 4腹腔注射给药能显著抑制鼠迟发型超敏反应 ,ED5 0 2 mg/ kg,至少比 Cs A强 15倍 ;使鼠胸腺明显萎缩 ED5 0 0 .3mg/ kg,比 Cs A强 10 0倍 ;显著抑制鼠局部移植物抗宿主反应 ED5 0 3mg/ kg,至少比 Cs A强 10倍。结果提示 F90 4是优于 Cs

The immunosuppressant F90 4 is a triene macrolide produced by Streptomyces hygroscopicus FC90 4 . The chemical structure and physico- chemical properties of F90 4 were identified as sirolimus ( rapamycin) ,a potent new immunosuppressant. The immunosuppressant F90 4 inhibited lymphocyte proliferation stimulated with PHA,Con A,LPS with an IC50 value of less than 0 . 1,1～ 10 ,1nmol/ Lrespectively.Intraperitoneal injection of F90 4 strongly suppressed both the DTH response to DNCB in mice ( ED50 2 mg/kg) and Gv HR induced by the injection of allogenic cells in mice ( ED50 3mg/kg) . Immunosuppressive activities of F90 4 was more potent than cyclosporin( Cs A) both in vitro and in vivo.