Steroidal and nonsteroidal drugs in endotoxin-induced uveitis.
Steroidal and nonsteroidal drugs in endotoxin-induced uveitis.
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DOI：
10.1089/jop.1994.10.329
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
P. Kulkarni
中科院分区：
文献类型：
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作者：
P. Kulkarni
在兔内毒素诱导的葡萄膜炎模型中测试了各种类型的抗炎化合物如类固醇（地塞米松）、环氧合酶抑制剂（吲哚美辛和氟比洛芬）、5-脂氧合酶抑制剂（BWA 218 C和BWA 4C）、免疫抑制剂（环孢菌素和雷帕霉素）和鱼肝油的抗炎活性。根据两种炎症反应评估眼内炎症，即血-房水屏障（BAB）的破坏和白细胞浸润到房水和虹膜睫状体（ICB）中。同时测定前列腺素（PG）E2和白三烯（LT）B4释放到房水中的量。吲哚美辛显着抑制PGE 2释放，而不影响白细胞或BAB反应。氟比洛芬阻止白细胞、PGE 2和LTB 4释放到房水中，但不阻止ICB趋化性。BWA 218 C和BWA 4C也显著抑制白细胞和LTB 4释放，但不抑制BAB反应。地塞米松（2 mg/kg，i.m.）和环孢菌素A（25 mg/kg i.m.）显著抑制白细胞向眼房和ICB的浸润和PGE 2的释放，但不能抑制BAB和LTB 4的释放。另一方面，雷帕霉素（10 mg/kg i.m.）和鱼肝油（每天1 ml，i.m.长达15天）显著阻止白细胞和BAB应答。鱼肝油也显着抑制PGE 2和LTB 4的释放，但雷帕霉素只影响PGE 2释放到房水。它的结论是，花生四烯酸代谢产物可能不会发挥至关重要的作用，在这种葡萄膜炎模型和额外的促炎介质，如细胞因子可能参与。
Various classes of anti-inflammatory compounds like steroids (dexamethasone), cyclooxygenase inhibitors (indomethacin and flurbiprofen), 5-lipoxygenase inhibitors (BWA 218C and BWA 4C), immunosuppressive drugs (cyclosporin and rapamycin) and cod liver oil were tested for their antiinflammatory activities in endotoxin-induced uveitis model in rabbits. Intraocular inflammation was assessed in terms of two inflammatory responses i.e. breakdown of blood-aqueous barrier (BAB) and leukocyte infiltration into aqueous humor and iris ciliary body (ICB). Prostaglandin (PG) E2 and leukotriene (LT) B4 release into aqueous humor was also measured. Indomethacin significantly inhibited PGE2 release without affecting leukocyte or BAB response. Flurbiprofen prevented leukocyte, PGE2 and LTB4 release into aqueous humor but not ICB chemotaxis. BWA 218C and BWA 4C also significantly inhibited leukocyte and LTB4 release but not BAB responses. Dexamethasone (2mg/kg, i.m.) and cyclosporin A (25 mg/kg i.m.) significantly inhibited leukocyte infiltration into aqueous humor and ICB, and PGE2 release but they failed to inhibit breakdown of BAB and LTB4 release. On the other hand, rapamycin (10mg/kg i.m.) and cod liver oil (1 ml daily i.m. up to 15 days) significantly prevented leukocyte and BAB response. Cod liver oil also significantly inhibited PGE2 and LTB4 release but rapamycin affected only PGE2 release into aqueous humor. It is concluded that arachidonic acid metabolites may not play a vital role in this uveitis model and additional proinflammatory mediators like cytokines may be involved.