Laquinimod (LAQ) is an effective immunomodulator, which is currently under development in phase III trials for the treatment of multiple sclerosis as an oral therapy.

Laquinimod在0.1-1 μM浓度下对外周血单核细胞（PBMC）的活性无影响。通过对健康受试者和复发性缓解型多发性硬化症（RRMS）患者的PBMC进行大规模基因表达微阵列分析，发现Laquinimod能够抑制与抗原呈递及相应炎症途径相关的基因表达。Laquinimod激活CD14+和CD4+细胞的Th2反应，并抑制CD8+细胞的增殖。Laquinimod通过抑制抗原呈递机制以及降低趋化性和粘附性，对免疫调节具有显著效果，并且通过抑制NF-κB途径显著地发挥抗炎作用，从而导致免疫竞争细胞的凋亡激活。[5]

Laquinimod（0.16-16 mg/kg/day）的给药剂量依赖性地抑制Lewis大鼠实验性自身免疫性神经炎（EAN）的发生率，改善临床症状，抑制P0肽180-199特异性T细胞反应以及外周神经的炎症和脱髓鞘，表明Laquinimod可能通过调节Th1/Th2细胞因子平衡发挥作用。[1] Laquinimod显著抑制小鼠急性实验性自身免疫性脑脊髓炎（EAE）的发展，其效力约为免疫调节剂roquinimex的20倍。[2] Laquinimod处理以剂量依赖方式抑制Lewis大鼠EAE的发展，并与roquinimex（Linomide）相比显示出更好的疾病抑制效果。[3] Laquinimod强力抑制IFN-beta k.o.小鼠和野生型小鼠慢性实验性自身免疫性脑脊髓炎（chEAE）的发展。[4] Laquinimod减少C57BL/6小鼠通过MOG(35-55)肽诱发的活跃EAE的临床症状、炎症和脱髓鞘，并下调VLA-4介导的黏附性和如IL-17的促炎细胞因子。[6] 在缺乏髓糖基细胞和T细胞中脑源性神经营养因子（BDNF）表达的条件性BDNF敲除小鼠（LLF小鼠）EAE模型的Laquinimod研究表明，Laquinimod还通过诱导脑源性神经营养因子（BDNF）调节自身免疫性脱髓鞘。[7]

The peripheral blood mononuclear cells (PBMC) are incubated with Laquinimod for 24 hours. Cell viability is measured on total PBMC by propidium iodide (PI) staining using an automated cell counter. Protein expression level is assessed in PBMC samples by Western blot using anti-HLA-DQA/DQB monoclonal antibodies.(Only for Reference)