Laboratório de Dermatologia e Imunodeficiência, Departamento de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Mem Inst Oswaldo Cruz. 2010 Feb;105(1):25-32. doi: 10.1590/s0074-02762010000100003.
The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro and anti-inflammatory activity. We investigated the expression of inflammatory cells and cytokines in the liver and serum of 51 chronically HCV infected patients and compared them to data from two sets of normal controls: 51 healthy blood donors and 33 liver biopsies of healthy liver donors. We also assessed the relationship between selected cytokines and cell populations in hepatic compartments and the disease stage. Compared with controls, hepatitis C patients had a greater expression of portal TNF-alpha, TGF-beta and CD4(+) and acinar IFN-gamma, TNF-alpha, IL-1beta and IL-4, as well as a higher serum concentration of IL-2, IL-10 and TGF-beta. Significant positive correlations were found between portal CD4+ and TNF-alpha, portal CD8(+) and TGF-beta, portal CD45(+)RO and TNF-alpha, acinar CD45(+)RO and IFN-gamma and acinar CD57(+) and TGF-beta. In conclusion, we have shown that (i) in this sample of predominantly mild disease, the immune response was associated with a pro-inflammatory response pattern, (ii) CD4(+) T-lymphocytes played a major role in orchestrating the immune response and (iii) these events primarily took place in the portal space.
慢性丙型肝炎病毒 (HCV) 感染的免疫发病机制是一个极具争议的问题，有人提出它涉及到具有促炎和抗炎活性的细胞因子之间的复杂平衡。我们研究了 51 例慢性 HCV 感染患者肝脏和血清中炎症细胞和细胞因子的表达情况，并将其与两组正常对照数据进行了比较：51 例健康献血者和 33 例健康肝活检供体。我们还评估了肝内细胞群中选定细胞因子与细胞群体之间的关系及其与疾病阶段的关系。与对照组相比，丙型肝炎患者的门脉 TNF-α、TGF-β和 CD4+以及腺泡 IFN-γ、TNF-α、IL-1β和 IL-4表达增加，血清中 IL-2、IL-10 和 TGF-β浓度也升高。我们发现门脉 CD4+与 TNF-α、门脉 CD8+与 TGF-β、门脉 CD45+RO 与 TNF-α、腺泡 CD45+RO 与 IFN-γ以及腺泡 CD57+与 TGF-β之间存在显著的正相关关系。总之，我们表明（i）在这个主要为轻度疾病的样本中，免疫反应与促炎反应模式相关，（ii）CD4+T 淋巴细胞在协调免疫反应中起主要作用，（iii）这些事件主要发生在门脉区。
