In vitro effect of thymosin-α1 and interferon-α on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C
In vitro effect of thymosin-α1 and interferon-α on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C
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DOI：
10.1046/j.1365-2893.2001.00285.x
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发表时间：
2001-05-01
影响因子：
2.5
通讯作者：
Bernardi, M
中科院分区：
文献类型：
--
作者：
Andreone, P;Cursaro, C;Bernardi, M
目前的证据表明，Th 1相关细胞因子的表达增加对于免疫介导的丙型肝炎感染的根除是重要的，而Th 2相关细胞因子的增加与感染的持续性有关。在这项研究中，我们评估了胸腺素-α 1（TA 1），一种天然存在的胸腺肽，和干扰素-α（IFN-α）对未经治疗的慢性丙型肝炎患者外周血单核细胞中细胞因子产生的影响。我们检测了与TA 1、IFN-α或两者一起孵育对Th 1相关细胞因子（IL-2、IFN-γ）、Th 2相关细胞因子（IL-4、IL-10）的产生以及抗病毒蛋白2 '，5'-寡腺苷酸合成酶的合成的影响。TA 1处理诱导IL-2和2 '，5'-寡腺苷酸合成酶的产生显著增加。在用IFN-α处理后也观察到较小的增加，而用TA 1和IFN-α一起孵育导致累加或协同效应。与TA 1孵育导致IL-4和IL-10减少，而IFN-α增加这些细胞因子。向IFN-α中加入TA 1显著逆转了这种IFN-α诱导的增加。因此，TA 1治疗可以通过增加Th 1型应答（持续清除丙型肝炎的基础）和减少Th 2型应答（与病毒血症持续相关）使丙型肝炎感染患者受益。
Current evidence suggests that increased expression of Th1-associated cytokines is important for immune-mediated eradication of hepatitis C infection, while an increase in Th2-associated cytokines is associated with persistence of infection. In this study we evaluated the effects of thymosin-alpha1 (TA1), a naturally occurring thymic peptide, and interferon-alpha (IFN-alpha) on cytokine production in peripheral blood mononuclear cells from untreated patients with chronic hepatitis C. We examined the effect of incubation with TA1, IFN-alpha, or both, on production of Th1-associated cytokines (IL-2, IFN-gamma), Th2-associated cytokines (IL-4, IL-10), and synthesis of the antiviral protein 2',5'-oligoadenylate synthetase. TA1 treatment induced a significant increase in production of IL-2 and 2',5'-oligoadenylate synthetase. Smaller increases were also seen after treatment with IFN-alpha, while incubation with TA1 and IFN-alpha together led to an additive or synergistic effect. Incubation with TA1 resulted in a decrease in IL-4 and IL-10, whereas IFN-alpha increased these cytokines. The addition of TA1 to IFN-alpha significantly reversed this IFN-alpha -induced increase. Hence, TA1 treatment could benefit patients with hepatitis C infection by increasing the Th1-type response, fundamental for sustained clearance of hepatitis C; and by decreasing the Th2-type response, associated with persistence of viraemia.