Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis
Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis
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DOI：
10.1191/1352458504ms1070oa
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发表时间：
2004-01-01
影响因子：
5.8
通讯作者：
Itoyama, Y
中科院分区：
文献类型：
--
作者：
Feng, J;Misu, T;Itoyama, Y
我们研究了非选择性磷酸二酯酶抑制剂异丁司特在临床应用剂量(60 mg/d)的免疫调节作用。在多发性硬化症(MS)患者中)。灵敏的实时定量聚合酶链式反应检测外周血中的细胞因子mRNA显示，异丁司特单药治疗显著降低了肿瘤坏死因子-α和干扰素(干扰素)-γ的信使核糖核酸和干扰素-γ/白介素4的信使核糖核酸的比值显著降低，提示细胞因子谱从Th1为主向Th2为主转变。在流式细胞仪分析中，自然杀伤T细胞，已被报道与多发性硬化症及其动物模型(实验性自身免疫性脑脊髓炎)的Th2反应有关，治疗后显著增加。在健康受试者或未经治疗的多发性硬化症患者中，没有发现明显的免疫学变化。异丁司特可能是治疗多发性硬化症的一种有前景的治疗方法，其临床疗效值得进一步研究。
We investigated the immunoregulatory effects of ibudilast, a nonselective phosphodiesterase inhibitor, at a clinically applicable dose ( 60 mg/day p.o. for four weeks) in multiple sclerosis ( MS) patients. Sensitive real-time PCR for quantifying cytokine mRNA in the blood CD4+ cells revealed that the ibudilast monotherapy significantly reduced tumour necrosis factor-alpha and interferon (IFN)-gamma mRNA and the IFN-gamma/interleukin-4 mRNA ratio, suggesting a shift in the cytokine profile from Th1 toward Th2 dominancy. In a flow cytometric analysis, natural killer T cells, which have been reported to relate to Th2 responses in MS and its animal model ( experimental autoimmune encephalomyelitis), increased significantly after the therapy. None of the significant immunological changes were seen in healthy subjects or untreated MS patients. Ibudilast may be a promising therapy for MS and its clinical effects warrant further study.