Hayden F G, Fritz R, Lobo M C, Alvord W, Strober W, Straus S E
University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
J Clin Invest. 1998 Feb 1;101(3):643-9. doi: 10.1172/JCI1355.
To further understand the role of cytokine responses in symptom formation and host defenses in influenza infection, we determined the levels of IL-1beta, IL-2, IL-6, IL-8, IFN-alpha, TGF-beta, and TNF-alpha in nasal lavage fluid, plasma, and serum obtained serially from 19 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) and correlated these levels with various measures of infection and illness severity. We found that IL-6 and IFN-alpha levels in nasal lavage fluids peaked early (day 2) and correlated directly with viral titers, temperature, mucus production, and symptom scores. IL-6 elevations were also found in the circulation at this time point. In contrast, TNF-alpha responses peaked later (day 3 in plasma, day 4 in nasal fluids), when viral shedding and symptoms were subsiding. Similarly, IL-8 peaked late in the illness course (days 4-6) and correlated only with lower respiratory symptoms, which also occurred late. None of IL-1beta, IL-2, or TGF-beta levels increased significantly. These data implicate IL-6 and IFN-alpha as key factors both in symptom formation and host defense in influenza.
为了进一步了解细胞因子反应在流感感染的症状形成和宿主防御中的作用，我们测定了19名经实验感染甲型流感病毒/得克萨斯/36/91（H1N1）的志愿者连续采集的鼻腔灌洗液、血浆和血清中白细胞介素-1β（IL-1β）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、干扰素-α（IFN-α）、转化生长因子-β（TGF-β）和肿瘤坏死因子-α（TNF-α）的水平，并将这些水平与感染和疾病严重程度的各种指标相关联。我们发现，鼻腔灌洗液中的IL-6和IFN-α水平在早期（第2天）达到峰值，并且与病毒滴度、体温、黏液分泌和症状评分直接相关。在这个时间点，循环系统中也发现了IL-6水平升高。相比之下，TNF-α反应在后期达到峰值（血浆中为第3天，鼻腔灌洗液中为第4天），此时病毒排出和症状正在消退。同样，IL-8在病程后期（第4 - 6天）达到峰值，并且仅与下呼吸道症状相关，而下呼吸道症状也出现在后期。IL-1β、IL-2或TGF-β水平均未显著升高。这些数据表明IL-6和IFN-α是流感症状形成和宿主防御中的关键因素。
