磷酸二酯酶抑制剂对丝裂原刺激的人外周血单个核细胞中Th1样和Th2样细胞因子产生的调节作用。

Modulation of Th1- and Th2-like cytokine production from mitogen-stimulated human peripheral blood mononuclear cells by phosphodiesterase inhibitors.

Yoshimura T, Nagao T, Nakao T, Watanabe S, Usami E, Kobayashi J, Yamazaki F, Tanaka H, Inagaki N, Nagai H

Pharmaceutical Division, Ogaki Municipal Hospital, Gifu, Japan.

Gen Pharmacol. 1998 Feb;30(2):175-80. doi: 10.1016/s0306-3623(97)00103-1.

Abstract

Effects of phosphodiesterase (PDE) inhibitors on the production of IFN-gamma, IL-2, IL-4 and IL-5 by phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) were investigated. In addition, we investigated the effects of dibutyrylcyclic AMP (dbcAMP) and a beta-adrenoceptor agonist on production of these cytokines. 2. Type IV, type III and nonselective PDE inhibitors were effective at inhibiting the production of IFN-gamma and IL-2 production in a dose-dependent manner. In contrast, IL-4 and IL-5 production was inhibited by only the highest concentration of type IV inhibitor, and other agents had no effect on the production. 3. Similarly, dbcAMP inhibited the production of IFN-gamma and IL-2 more potently than IL-4 and IL-5. 4. The addition of a beta-adrenoceptor agonist increased the inhibitory effect of PDE inhibitors tested on the production of IFN-gamma and IL-2. 5. These results indicate that PDE inhibitors or cAMP-elevating agents modulate Th1 cytokine more effectively than Th2 cytokine production.

摘要

研究了磷酸二酯酶（PDE）抑制剂对植物血凝素（PHA）刺激的人外周血单个核细胞（PBMC）产生干扰素-γ、白细胞介素-2、白细胞介素-4和白细胞介素-5的影响。此外，我们还研究了二丁酰环磷腺苷（dbcAMP）和β-肾上腺素能受体激动剂对这些细胞因子产生的影响。2. IV型、III型和非选择性PDE抑制剂均能以剂量依赖的方式有效抑制干扰素-γ的产生和白细胞介素-2的产生。相比之下，只有最高浓度的IV型抑制剂能抑制白细胞介素-4和白细胞介素-5的产生，其他药物对其产生没有影响。3. 同样，dbcAMP对干扰素-γ和白细胞介素-2产生的抑制作用比对白细胞介素-4和白细胞介素-5更有效。4. 添加β-肾上腺素能受体激动剂可增强所测试的PDE抑制剂对干扰素-γ和白细胞介素-2产生的抑制作用。5. 这些结果表明，PDE抑制剂或升高cAMP的药物对Th1细胞因子的调节作用比对Th2细胞因子的产生更有效。