Pettipher E R, Eskra J D, Labasi J M
Central Research Division, Pfizer Inc., Groton, CT, 06340, USA.
Cytokine. 1997 Aug;9(8):582-6. doi: 10.1006/cyto.1997.0205.
Intraperitoneal administration of the phosphodiesterase type 4 (PDE4) inhibitor rolipram (1-30 mg/kg) caused a dose-dependent increase in the circulating levels of both corticosterone and adrenaline in male Balb/c mice. These increases were maximal 0.5-1 h after administration of rolipram and had declined to control levels by 4 h. Rolipram (10 mg/kg i.p.) substantially inhibited the production of tumour necrosis factor alpha (TNF-alpha) ex vivo in blood from normal mice but was ineffective in adrenalectomized mice, suggesting that the inhibitory effect of rolipram is dependent on intact adrenal function. The corticosterone antagonist, RU 486, and the beta-adrenoceptor antagonist, propranolol, both partially reversed the inhibitory activity of rolipram while the combination of RU 486 and popranolol abrogated the effect of the rolipram to the same degree as adrenalectomy. These data suggest the release of both corticosterone and adrenaline contribute to the ability of rolipram to inhibit TNF-alpha production in mouse blood ex vivo.
对雄性Balb/c小鼠腹腔注射磷酸二酯酶4（PDE4）抑制剂咯利普兰（1 - 30毫克/千克），可使皮质酮和肾上腺素的循环水平呈剂量依赖性升高。这些升高在注射咯利普兰后0.5 - 1小时达到最大值，并在4小时后降至对照水平。咯利普兰（10毫克/千克腹腔注射）可显著抑制正常小鼠血液中肿瘤坏死因子α（TNF-α）的体外产生，但对肾上腺切除的小鼠无效，这表明咯利普兰的抑制作用依赖于完整的肾上腺功能。皮质酮拮抗剂RU 486和β-肾上腺素能受体拮抗剂普萘洛尔均可部分逆转咯利普兰的抑制活性，而RU 486和普萘洛尔的组合则与肾上腺切除一样，同等程度地消除了咯利普兰的作用。这些数据表明，皮质酮和肾上腺素的释放均有助于咯利普兰在体外抑制小鼠血液中TNF-α产生的能力。
