Arad G, Katzenellenbogen M, Levy R, Slavin S, Kaempfer R
Department of Molecular Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Int Immunol. 1996 Oct;8(10):1603-7. doi: 10.1093/intimm/8.10.1603.
Linomide (LS-2616, quinoline-3-carboxamide) has strong immunomodulating effects in animal models, inhibiting toxic shock, progressive autoimmune disease and cancer. In humans, linomide strongly reduced the appearance of new lesions in multiple sclerosis yet enhanced immune responses after bone marrow transplantation. In contrast to these clear effects in vivo, attempts to show an effect of linomide in vitro have not been successful and its mode of action remains to be elucidated. Here we show that at concentrations effective in vivo, linomide is active on human peripheral blood mononuclear cells (PBMC), severely inhibiting the induction by Staphylococcus aureus enterotoxin B of mRNA of three cytokine genes expressed in Th1 cells, those for IFN-gamma, IL-2, and tumor necrosis factor-beta. Yet, cell viability was not affected by linomide. The extent of inhibition is dose-dependent on linomide. Linomide also blocked induction of IL-2 and IFN-gamma mRNA by phytohemagglutinin. The inhibitory effect is expressed immediately but can be enhanced significantly by a prolonged exposure of PBMC to linomide, reaching 10-fold. These results support the concept that linomide antagonizes the activation of Th1 cells during a cellular immune response.
利诺米德（LS - 2616，喹啉 - 3 - 甲酰胺）在动物模型中具有强大的免疫调节作用，可抑制中毒性休克、进行性自身免疫性疾病和癌症。在人体中，利诺米德能显著减少多发性硬化症新病灶的出现，但在骨髓移植后可增强免疫反应。与在体内的这些明确作用相反，在体外显示利诺米德作用的尝试尚未成功，其作用方式仍有待阐明。在此我们表明，在体内有效的浓度下，利诺米德对人外周血单个核细胞（PBMC）具有活性，严重抑制金黄色葡萄球菌肠毒素B对Th1细胞中表达的三种细胞因子基因（即干扰素 - γ、白细胞介素 - 2和肿瘤坏死因子 - β）mRNA的诱导。然而，细胞活力不受利诺米德影响。抑制程度呈利诺米德剂量依赖性。利诺米德还可阻断植物血凝素对白细胞介素 - 2和干扰素 - γ mRNA的诱导。抑制作用立即显现，但通过将PBMC长时间暴露于利诺米德可显著增强，可达十倍。这些结果支持了利诺米德在细胞免疫反应过程中拮抗Th1细胞活化这一概念。
