Immunoregulatory cytokines in chronic hepatitis C virus infection: Pre- and posttreatment with interferon alfa
Immunoregulatory cytokines in chronic hepatitis C virus infection: Pre- and posttreatment with interferon alfa
复制标题
DOI：
10.1053/jhep.1996.v24.pm0008707283
复制
发表时间：
1996-07-01
期刊：
影响因子：
13.5
通讯作者：
Krams, SM
中科院分区：
文献类型：
--
作者：
Cacciarelli, TV;Martinez, OM;Krams, SM
T淋巴细胞和免疫调节细胞因子可能在宿主对丙型肝炎病毒感染的反应中起重要作用。T辅助细胞1型(Th1)细胞因子(IL-2、干扰素-γ)是宿主抗病毒免疫反应所必需的，包括细胞毒性T细胞的产生和自然杀伤细胞的激活，而T辅助细胞2型(Th2)细胞因子(IL-4、IL-10)可以抑制这些效应机制的发展。本研究检测了23例丙型肝炎患者血清中Th1、Th2细胞因子水平，并与生化指标(丙氨酸氨基转移酶[ALT])和病毒(HCVRNA)指标进行比较。对11例患者在干扰素治疗期间和治疗后1周、12周和1周(n=33)进行了系列细胞因子水平测定。丙型肝炎患者外周血中IL-2、IL-4、IL-10和干扰素-γ水平显著高于正常对照组(分别为128pg/mLvs.25pg/mL3,045vs29pg/mL2,949vs18pg/mL307vs24pg/mLP<；0.01)。干扰素-α治疗降低了IL-4(321+/-224 pg/m L)和IL-10(1,011+/-344 pg/m l)水平，这与丙型肝炎病毒核糖核酸(114+/-27 vs.25+/-20 eq/m L x 10(5)，干扰素-α治疗前后[12周]；P<；0.05)的下降是平行的。这些发现表明，在丙型肝炎患者中存在活化的T细胞反应，表现为循环免疫调节细胞因子的增加。此外，干扰素-α治疗会降低Th2细胞因子的反应。因此，调节T细胞功能和细胞因子的产生可能是干扰素-α治疗降低病毒负担的机制之一。
T lymphocytes and immunoregulatory cytokines may be important in the host response to hepatitis C virus (HCV) infection. T-helper type 1 (Th1) cytokines (interleukin [IL]-2, interferon gamma [IFN-gamma]) are required for host antiviral immune responses, including cytotoxic T-cell generation and natural killer cell activation, while T-helper type 2 (Th2) cytokines (IL-4, IL-10) can inhibit the development of these effector mechanisms. in this study, the serum levels of Th1 and Th2 cytokines in patients (n = 23) infected with HCV were measured and compared with biochemical (alanine transaminase [ALT]) and viral (HCV RNA) indicators of infection. Serial cytokine levels were measured in a subset of 11 patients at 1 and 12 weeks during and at 1 week after interferon alfa (IFN-alpha) therapy (n = 33 samples). Levels of circulating IL-2, IL-4, IL-10, and IFN-gamma were significantly elevated in HCV patients versus normal controls (128 vs. 25 pg/mL, 3,045 vs. 29 pg/mL, 2,949 vs. 18 pg/mL, and 307 vs. 24 pg/mL, respectively; P < .01). Treatment with IFN-alpha decreased the levels of IL-4 (321 +/- 224 pg/mL) and IL-10 (1,011 +/- 344 pg/mL), which paralleled a decrease in HCV RNA (114 +/- 27 vs. 25 +/- 20 Eq/mL x 10(5), pre- vs. post-IFN-alpha [12 weeks]; P < .05). These findings indicate that an activated T cell response, as manifest by increased circulating immunoregulatory cytokines, is present in patients with HCV liver disease. Furthermore, treatment with IFN-alpha diminishes the Th2 cytokine response. Thus, modulation of T-cell function and cytokine production may be one mechanism whereby IFN-alpha therapy results in reduced viral burden.