Matsui Eiko, Shinoda Shinji, Fukutomi Osamu, Kaneko Hideo, Fukao Toshiyuki, Kondo Naomi
Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Exp Ther Med. 2010 Nov;1(6):977-982. doi: 10.3892/etm.2010.149. Epub 2010 Sep 15.
Although currently available antiasthmatic drugs are effective for many patients with bronchial asthma, some patients do not respond well to medications or exhibit more frequent adverse effects compared to other patients. Antiasthmatic treatment should be tailored individually according to the predispositions and pathophysiological conditions of patients. No reports have been made concerning the relationships between the effects of Th2 cytokine inhibitors and gene polymorphisms. The present study was therefore performed to investigate the relationships between gene polymorphisms known to be involved in allergy and cytokine production in peripheral blood mononuclear cells and the clinical efficacy of suplatast tosilate, a Th2 cytokine inhibitor, to clarify factors determining responses to treatment. A total of 20 children were enrolled in the study. The children were enrolled in a run-in period of 2 weeks and then received suplatast tosilate orally for 8 weeks. The children or their parents were instructed to keep an asthma diary to record changes in signs/symptoms of bronchial asthma before and after treatment. Concentrations of interferon (IFN)-γ and interleukin (IL)-4 in the supernatant were determined using ELISA methods. Using the invader assay method, the genotypes of polymorphisms of the genes were determined. Treatment with suplatast tosilate was more effective in children without the -444 A/C polymorphism of the LTC4 synthase gene and in children without the IL-13 variant R110Q. In children who responded well, production of IFN-γ was significantly increased after treatment. In this study, responses to suplatast tosilate were associated with SNPs of the LTC4 synthase and IL-13 gene as well as change in the production of IFN-γ before and after drug administration.
尽管目前可用的抗哮喘药物对许多支气管哮喘患者有效，但一些患者对药物反应不佳，或与其他患者相比表现出更频繁的不良反应。抗哮喘治疗应根据患者的易感性和病理生理状况进行个体化调整。关于Th2细胞因子抑制剂的效果与基因多态性之间的关系尚无报道。因此，本研究旨在调查已知参与过敏和外周血单个核细胞中细胞因子产生的基因多态性与Th2细胞因子抑制剂甲苯磺酸舒普拉泰的临床疗效之间的关系，以阐明决定治疗反应的因素。共有20名儿童参与了该研究。这些儿童先进入为期2周的导入期，然后口服甲苯磺酸舒普拉泰8周。指导儿童或其父母记录哮喘日记，以记录治疗前后支气管哮喘体征/症状的变化。使用ELISA方法测定上清液中干扰素（IFN）-γ和白细胞介素（IL）-4的浓度。使用侵入检测法测定基因多态性的基因型。甲苯磺酸舒普拉泰治疗对无白三烯C4合酶基因-444 A/C多态性的儿童和无IL-13变体R110Q的儿童更有效。在反应良好的儿童中，治疗后IFN-γ的产生显著增加。在本研究中，对甲苯磺酸舒普拉泰的反应与白三烯C4合酶和IL-13基因的单核苷酸多态性以及给药前后IFN-γ产生的变化有关。
