Nain M, Hinder F, Gong J H, Schmidt A, Bender A, Sprenger H, Gemsa D
Institute of Immunology, Philipps University, Marburg, West Germany.
J Immunol. 1990 Sep 15;145(6):1921-8.
Influenza A virus infections are commonly associated with symptoms that suggest involvement of TNF-alpha. In this study, we exposed human monocytes, rat alveolar macrophages, and murine PU5-1.8 macrophages to influenza A virus, strain Puerto Rico 8. We observed a productive infection that was accompanied by TNF-alpha mRNA accumulation, TNF-alpha release and subsequent cell death. TNF-alpha production was dependent on exposure to live virus, in contrast to IFN release that was also induced by UV-inactivated virus. Most strikingly, low amounts of LPS (1 to 10 ng/ml) from Escherichia coli or Haemophilus influenzae were capable of strongly potentiating TNF-alpha production from virus-infected macrophages. The potentiating effect of LPS was neither due to increased survival of macrophages nor to altered virus multiplication, enhanced TNF-alpha gene expression, discharge of intracellular TNF-alpha stores, or shifts in the kinetics of TNF-alpha release. Thus, low amounts of LPS, which could easily be present in vivo, may serve as a potent trigger signal for TNF-alpha production from macrophages that have been primed by influenza A virus infection. These data suggest that the frequently observed serious complications of combined influenza A virus and bacterial infections may be partially due to a high TNF-alpha production.
甲型流感病毒感染通常伴有提示肿瘤坏死因子-α（TNF-α）参与的症状。在本研究中，我们将人单核细胞、大鼠肺泡巨噬细胞和小鼠PU5-1.8巨噬细胞暴露于甲型流感病毒波多黎各8株。我们观察到一次有活性的感染，伴随有TNF-α mRNA积累、TNF-α释放及随后的细胞死亡。与紫外线灭活病毒也能诱导的干扰素释放不同，TNF-α的产生依赖于活病毒暴露。最显著的是，来自大肠杆菌或流感嗜血杆菌的低剂量脂多糖（LPS，1至10 ng/ml）能够强烈增强病毒感染巨噬细胞的TNF-α产生。LPS的增强作用既不是由于巨噬细胞存活率增加，也不是由于病毒增殖改变、TNF-α基因表达增强、细胞内TNF-α储存释放或TNF-α释放动力学改变。因此，体内容易存在的低剂量LPS可能作为甲型流感病毒感染致敏的巨噬细胞产生TNF-α的有效触发信号。这些数据表明，甲型流感病毒和细菌合并感染时经常观察到的严重并发症可能部分归因于TNF-α的高产生。
