Geissler M, Gesien A, Wands J R
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown 02129, USA.
Hepatology. 1997 Sep;26(3):764-70. doi: 10.1002/hep.510260332.
Hepatitis B virus (HBV) is common in alcoholics and may result in chronic infection. Persistence of HBV infection could be partially caused by the effects of ethanol on the cellular and humoral immune response to viral structural proteins. The DNA-based immunization approach was used to experimentally assess the effects of chronic ethanol feeding on immune responses directed against the middle envelope protein (MHBs) of HBV. Mice were fed an ethanol or isocaloric, pair-fed control liquid diet for 8 weeks, followed by immunization with a plasmid construct containing the pre-S2/S gene that encodes for MHBs. Chronic ethanol consumption marginally reduced the levels of the antibody to hepatitis B surface proteins (anti-HBs) generated by the DNA-based immunization approach. Initially, cytotoxic lymphocyte (CTL) activity was higher in ethanol-fed mice but progressively declined following the second and third immunizations as compared with control mice. In addition, CTL and CD4+ T helper (TH) cells responded poorly to increasing concentrations of envelope protein and peptides in vitro with respect to generation of CTL activity and proliferative responses. Finally, proliferating CD4+ T cells derived from ethanol-fed animals had substantial changes in the levels of cytokines secreted into the culture supernatants as compared with control mice. These studies show that chronic ethanol consumption substantially alters the cellular immune responses to a human viral structural protein, and that these effects may contribute to the persistence of viral infection.
乙型肝炎病毒（HBV）在酗酒者中很常见，可能导致慢性感染。HBV感染的持续存在可能部分是由于乙醇对病毒结构蛋白的细胞免疫和体液免疫反应的影响。基于DNA的免疫方法被用于实验评估长期喂食乙醇对针对HBV中包膜蛋白（MHBs）的免疫反应的影响。给小鼠喂食乙醇或等热量的配对喂养对照液体饮食8周，然后用含有编码MHBs的前S2/S基因的质粒构建体进行免疫。长期摄入乙醇略微降低了基于DNA的免疫方法产生的乙型肝炎表面蛋白抗体（抗-HBs）水平。最初，喂食乙醇的小鼠的细胞毒性淋巴细胞（CTL）活性较高，但与对照小鼠相比，在第二次和第三次免疫后逐渐下降。此外，CTL和CD4+辅助性T细胞（TH）在体外对包膜蛋白和肽浓度增加时产生CTL活性和增殖反应的反应较差。最后，与对照小鼠相比，来自喂食乙醇动物的增殖性CD4+ T细胞分泌到培养上清液中的细胞因子水平有显著变化。这些研究表明，长期摄入乙醇会显著改变对人类病毒结构蛋白的细胞免疫反应，并且这些影响可能有助于病毒感染的持续存在。
