D'Hellencourt C L, Diaw L, Cornillet P, Guenounou M
Laboratoire d'Hématologie, C.H.R. Robert Debré, Reims, France.
Int J Immunopharmacol. 1996 Dec;18(12):739-48. doi: 10.1016/s0192-0561(97)85556-7.
Pentoxifylline (PTX) is a methylxanthine drug known to inhibit the production of tumor necrosis factor-alpha (TNF alpha), which plays a key role in inflammation. Recent studies also revealed that other cytokines may be inhibited by PTX. We investigated PTX effects on production and mRNA expression of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta and IL-10. Cytokine release was studied in 1/10 diluted whole blood culture (WB) and in peripheral blood mononuclear cell (PBMC) culture. Cytokine production was triggered in both culture systems by endotoxin (LPS) or by phorbol ester (PMA) plus phytohemagglutinin (PHA). Our results showed that expression and production of TNF alpha and TNF beta were inhibited by PTX in a dose-dependent manner. Moreover, we observed that depending on the way of activating cells, PTX induced an up- or a down-regulation (in PMA + PHA or LPS stimulated cells, respectively) for IL-1 and IL-6 release. We also noted that the effects of PTX on IL-6, IL-8 and IL-10 production were different in WB and in PBMC culture. In conclusion PTX acts on cytokine in a complex manner depending on cellular environment and on the method of activation.
己酮可可碱（PTX）是一种甲基黄嘌呤类药物，已知其可抑制肿瘤坏死因子-α（TNF-α）的产生，而TNF-α在炎症中起关键作用。最近的研究还表明，PTX可能会抑制其他细胞因子。我们研究了PTX对TNF-α、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、肿瘤坏死因子-β（TNF-β）和白细胞介素-10（IL-10）产生及mRNA表达的影响。在1/10稀释的全血培养（WB）和外周血单核细胞（PBMC）培养中研究细胞因子释放。两种培养系统中，通过内毒素（LPS）或佛波酯（PMA）加植物血凝素（PHA）触发细胞因子产生。我们的结果表明，PTX以剂量依赖的方式抑制TNF-α和TNF-β的表达及产生。此外，我们观察到，根据激活细胞的方式，PTX分别在PMA + PHA或LPS刺激的细胞中诱导IL-1和IL-6释放上调或下调。我们还注意到，PTX对IL-6、IL-8和IL-10产生的影响在WB和PBMC培养中有所不同。总之，PTX根据细胞环境和激活方法以复杂的方式作用于细胞因子。
