Klemm P, Harris H J, Perretti M
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew's Hospital, London, UK.
Eur J Pharmacol. 1995 Jul 25;281(1):69-74. doi: 10.1016/0014-2999(95)00232-a.
Treatment of mice with rolipram, a phosphodiesterase type 4 inhibitor, selectively modified the acute inflammatory reaction elicited by zymosan administration in 6-day-old mouse air-pouches. Rolipram (1-10 mg kg-1, i.p.) prevented the rise of endogenous tumor necrosis factor-alpha (TNF-alpha) in the lavage fluids (approximately 60% inhibition) induced by zymosan, with no effect upon interleukin-1 alpha levels. This action was not accompanied by changes in neutrophil accumulation, but the amount of elastase released in the lavage fluids was significantly reduced (approximately 50%). Dexamethasone (1.5 mg kg-1, i.v.), used for comparative purposes, significantly reduced the release of TNF-alpha (> 50%), interleukin-1 alpha (> 70%) and cellular infiltration (approximately 50%), but had only a marginal effect on the release of elastase activity. In conclusion, in this murine model of acute inflammation induced by zymosan, rolipram inhibited the endogenous TNF-alpha production at a local site of inflammation, such as the subcutaneous air-pouch, and prevented the full activation of migrated cells.
用磷酸二酯酶4抑制剂咯利普兰治疗小鼠，可选择性改变6日龄小鼠气囊肿中酵母聚糖给药引发的急性炎症反应。咯利普兰（1 - 10毫克/千克，腹腔注射）可抑制酵母聚糖诱导的灌洗液中内源性肿瘤坏死因子-α（TNF-α）升高（约60%抑制率），而对白细胞介素-1α水平无影响。此作用未伴随中性粒细胞聚集的变化，但灌洗液中释放的弹性蛋白酶量显著减少（约50%）。用于比较的地塞米松（1.5毫克/千克，静脉注射）可显著降低TNF-α释放（> 50%）、白细胞介素-1α释放（> 70%）和细胞浸润（约50%），但对弹性蛋白酶活性释放仅有轻微影响。总之，在这个由酵母聚糖诱导的急性炎症小鼠模型中，咯利普兰在炎症局部部位（如皮下气囊肿）抑制内源性TNF-α产生，并阻止迁移细胞的完全激活。
