Ethanol Feeding Impairs Innate Immunity and Alters the Expression of Th1- and Th2-Phenotype Cytokines in Murine Klebsiella Pneumonia

The prolonged and excessive consumption of alcohol has been shown to predispose the host to a variety of infectious complications, which may be due, in part, to the inability to produce important activating cytokines. In this study, we assessed the effect of chronic alcohol ingestion on bacterial clearance, survival, and cytokine mRNA and protein expression in mice with Klebsiella pneumonia. Two-week ethanol feeding resulted in substantial impairment in the clearance of K. pneumoniae and decreased survival, compared with CD-1 mice receiving an isocaloric diet without ethanol. No differences were noted between control and ethanol groups in the total numbers or percent of bronchoalveolar lavage fluid neutrophils or macrophages at 24 and 48 hr post-intratracheal K. pneumoniae. Importantly, the lungs of alcohol-fed mice with Klebsiella pneumonia displayed a decrease or delay in the expression of interleukin (IL)-12 p35 and p40 mRNA and interferon-γ mRNA, respectively, as well as reduced IL-12 and interferon-γ protein levels, compared with controls. Conversely, a time-dependent increase in lung IL-10 mRNA and protein was noted in ethanol-fed animals, compared with control animals challenged with K. pneumoniae. In summary, our studies indicate that ethanol ingestion results in a profound suppression of lung bacterial clearance and decreased survival in Klebsiella pneumonia, which occurs in association with a shift in the balance of lung cytokine mRNA and protein expression favoring Th2- rather than Th1-phenotype cytokines.     

索磷布韦/维帕他韦联合利巴韦林治疗慢性丙型肝炎患者疗效临床研究

目的 探讨应用索磷布韦/维帕他韦联合利巴韦林治疗慢性丙型肝炎(CHC)患者的疗效及血清细胞毒性T淋巴细胞相关抗原4(CTLA-4)、肿瘤坏死因子α诱导蛋白8样分子2(TIPE2)和白介素-12(IL-12)水平的变化。方法 2018年5月~2019年5月我院肝病科就诊的105例CHC患者,采用随机数字表法将所选患者分为对照组51例和观察组54例,分别给予利巴韦林联合干扰素α-2b或者索磷布韦/维帕他韦联合利巴韦林治疗观察3个月。采用ELISA法检测血清CTLA-4、TIPE2和IL-12水平。结果 观察组快速病毒学应答(RVR)率为(88.9%,显著高于对照组(43.1%,P<0.05),早期病毒学应答(EVR)率为90.7%,显著高于对照组(52.9%,P<0.05),治疗结束时应答率为96.3%,显著高于对照组(76.5%,P<0.05),持续病毒学应答(SVR)率为92.6%,显著高于对照组(60.8%,P<0.05);外周血白细胞水平为(5.2±2.0)×10⁹/L,显著高于对照组【(3.4±1.8)×10⁹/L,P<0.05】,红细胞水平为(4.9±0.5)×10⁹/L,显著高于对照组【(4.6±0.7)×10⁹/L,P<0.05】,血小板计数为(113.2±38.6)×10⁹/L,显著高于对照组【(94.7±41.2)×10⁹/L,P<0.05】;血清CTLA-4水平为(1.1±0.4)ng/mL,显著低于对照组【(1.6±0.7)ng/mL,P<0.05】,血清IL-12水平为(29.6±7.3)pg/mL,显著低于对照组【(41.5±11.7)pg/mL,P<0.05】,而血清TIPE2水平为(0.8±0.1)μg/L,显著高于对照组【(0.6±0.3)μg/L,P<0.05】;在治疗期间,观察组不良反应发生率为25.9%,显著低于对照组(94.1%,P<0.05)。结论 应用索磷布韦/维帕他韦联合利巴韦林治疗CHC患者疗效好,除强大的抗病毒作用外,可能与该治疗能降低血清CTLA-4和IL-12水平,升高血清TIPE2水平有关。