Oda N, Minoguchi K, Tanaka A, Yokoe T, Minoguchi H, Matsuo H, Nakashima M, Tasaki T, Adachi M
First Department of Internal Medicine, Showa University, Tokyo, Japan.
Clin Exp Allergy. 2002 Dec;32(12):1782-6. doi: 10.1046/j.1365-2222.2002.01547.x.
Suplatast tosilate is an anti-allergic agent that suppresses cytokine production by human Th2 cells.
We investigated the effects of suplatast tosilate on the production of thymus- and activation-regulated chemokine (TARC) by T cells from allergic patients with asthma.
Purified protein derivative (PPD)-specific Th1 cell lines and Dermatophagoides farinae (Der f)-specific Th2 cell lines were established from nine patients with house dust mite-allergic asthma. The effects of suplatast tosilate on mRNA expression of TARC and protein production of TARC from antigen-specific Th1 or Th2 cell lines were investigated after stimulation with relevant antigens or phytohemagglutinin (PHA). In addition, the effects of IL-4, IL-10, and IFN-gamma on TARC production by Der f-specific Th2 cell lines in the presence or absence of suplatast tosilate were studied.
Although PPD-specific Th1 cell lines did not produce TARC after stimulation with PPD antigen or PHA, stimulation of Der f-specific Th2 cell lines with Der f antigen or PHA increased production of TARC. Suplatast tosilate significantly and dose-dependently inhibited production of TARC by Der f-specific Th2 cell lines stimulated with either Der f antigen (76.5% inhibition at 100 microg/mL, P < 0.01) or PHA (81.9% inhibition at 100 microg/mL, P < 0.01). TARC production by Der f-specific Th2 cell lines was significantly increased only by activation with IL-4 but not with IL-10 or IFN-gamma; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 microg/mL, P < 0.01).
Suplatast tosilate inhibits TARC production by human Th2 cells. Therefore, this agent inhibits both Th2 cytokine and Th2 chemokine and may be a useful anti-allergic agent.
托西酸舒普拉泰是一种抗过敏药物，可抑制人Th2细胞产生细胞因子。
我们研究了托西酸舒普拉泰对哮喘过敏患者T细胞产生胸腺和活化调节趋化因子（TARC）的影响。
从9例屋尘螨过敏性哮喘患者中建立纯化蛋白衍生物（PPD）特异性Th1细胞系和粉尘螨（Der f）特异性Th2细胞系。在用相关抗原或植物血凝素（PHA）刺激后，研究托西酸舒普拉泰对TARC mRNA表达和抗原特异性Th1或Th2细胞系TARC蛋白产生的影响。此外，研究了白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和干扰素-γ（IFN-γ）在有或无托西酸舒普拉泰存在的情况下对Der f特异性Th2细胞系产生TARC的影响。
虽然PPD特异性Th1细胞系在用PPD抗原或PHA刺激后不产生TARC，但用Der f抗原或PHA刺激Der f特异性Th2细胞系可增加TARC的产生。托西酸舒普拉泰显著且剂量依赖性地抑制用Der f抗原（100μg/mL时抑制76.5%，P<0.01）或PHA（100μg/mL时抑制81.9%，P<0.01）刺激的Der f特异性Th2细胞系产生TARC。Der f特异性Th2细胞系仅通过IL-4激活而非IL-10或IFN-γ激活显著增加TARC产生；托西酸舒普拉泰显著抑制了TARC产生的增加（100μg/mL时抑制97.5%，P<0.01）。
托西酸舒普拉泰抑制人Th2细胞产生TARC。因此，该药物同时抑制Th2细胞因子和Th2趋化因子，可能是一种有用的抗过敏药物。
