Kallinowski B, Haseroth K, Marinos G, Hanck C, Stremmel W, Theilmann L, Singer M V, Rossol S
Department of Gastroenterology, University of Heidelberg/Mannheim, Mannheim, Germany.
Clin Exp Immunol. 1998 Feb;111(2):269-77. doi: 10.1046/j.1365-2249.1998.00469.x.
There is evidence that TNF-alpha contributes to the pathogenesis of chronic viral hepatitis. The cellular effects of this cytokine are regulated by two specific receptors, and membranous shedding of these receptors reflects activation of the TNF system. We performed a study of TNF-alpha and functionally active soluble TNF-receptors (TNFR-p55 and -p75) in 105 patients with chronic HCV infection. In HCV RNA-positive patients a significant enhancement of TNF-alpha and both receptor types was observed compared with controls (TNF-alpha 83.8+/-91.7 pg/ml versus 18.8+/-8.4 pg/ml, P<0.001; TNFR-p55 1.4+/-0.4 ng/ml versus 0.9+/-0.2 ng/ml, P<0.0001; TNFR-p75 6.4+/-2.4 ng/ml versus 2.9+/-0.6 ng/ml, P<0.0001, respectively). The enhanced serum levels of TNF-alpha and TNFRs were reflected by a significant expression of TNFR-specific mRNA in peripheral mononuclear cells of HCV-infected patients (P<0.001). Serum aminotransferases correlated with soluble TNFR-p75 (P<0.001) but not with TNFR-p55 and TNF-alpha. We demonstrated an association of the degree of histological inflammation with both TNFRs (P<0.01). Furthermore, enhanced hepatocellular expression of TNF-alpha and TNFRs could be demonstrated by immunohistochemical staining in HCV-infected patients. Sixty-eight out of 105 patients were treated with interferon-alpha (IFN-alpha) (3x10(6)U x 3/week). Pretreatment levels of TNF-alpha and TNFRs did not differ between responders and non-responders. Our results demonstrate that TNF-alpha and TNFRs are enhanced in chronic HCV infection and reflect histological activity of the disease. This up-regulation of TNFRs might modify host response and potentially contribute to liver damage in chronic HCV infection.
有证据表明肿瘤坏死因子-α（TNF-α）在慢性病毒性肝炎的发病机制中起作用。这种细胞因子的细胞效应由两种特异性受体调节，这些受体的膜性脱落反映了TNF系统的激活。我们对105例慢性丙型肝炎病毒（HCV）感染患者的TNF-α和功能性活性可溶性TNF受体（TNFR-p55和TNFR-p75）进行了研究。与对照组相比，HCV RNA阳性患者的TNF-α以及两种受体类型均显著升高（TNF-α：83.8±91.7 pg/ml对18.8±8.4 pg/ml，P<0.001；TNFR-p55：1.4±0.4 ng/ml对0.9±0.2 ng/ml，P<0.0001；TNFR-p75：6.4±2.4 ng/ml对2.9±0.6 ng/ml，P<0.0001）。HCV感染患者外周血单个核细胞中TNFR特异性mRNA的显著表达反映了血清中TNF-α和TNFRs水平的升高（P<0.001）。血清转氨酶与可溶性TNFR-p75相关（P<0.001），但与TNFR-p55和TNF-α无关。我们证明组织学炎症程度与两种TNFR均相关（P<0.01）。此外，通过免疫组织化学染色可证明HCV感染患者肝细胞中TNF-α和TNFRs的表达增强。105例患者中有68例接受了α干扰素（IFN-α）治疗（3×10⁶U×3次/周）。治疗前，TNF-α和TNFRs水平在应答者和无应答者之间无差异。我们的结果表明，在慢性HCV感染中TNF-α和TNFRs升高，反映了疾病的组织学活性。TNFRs的这种上调可能会改变宿主反应，并可能导致慢性HCV感染中的肝损伤。
