Relationship between the benefits of suplatast tosilate, a Th2 cytokine inhibitor, and gene polymorphisms in children with bronchial asthma.

ABSTRACT

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.