Robbins Clinton S, Bauer Carla M T, Vujicic Neda, Gaschler Gordon J, Lichty Brian D, Brown Earl G, Stämpfli Martin R
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, ON, L8N 3Z5 Canada.
Am J Respir Crit Care Med. 2006 Dec 15;174(12):1342-51. doi: 10.1164/rccm.200604-561OC. Epub 2006 Oct 5.
Studies have shown that cigarette smoke impacts respiratory host defense mechanisms; however, it is poorly understood how these smoke-induced changes impact the overall ability of the host to deal with pathogenic agents.
The objective of this study was to investigate the impact of mainstream cigarette smoke exposure on immune inflammatory responses and viral burden after respiratory infection with influenza A.
C57BL/6 mice were sham- or smoke-exposed for 3 to 5 mo and infected with either 2.5 x 10(3) pfu (low dose) or 2.5 x 10(5) pfu (high dose) influenza virus.
Although smoke exposure attenuated the airway's inflammatory response to low-dose infection, we observed increased inflammation in smoke-exposed compared with sham-exposed mice after infection with high-dose influenza, despite a similar rate of viral clearance. The heightened inflammatory response was associated with increased expression of tumor necrosis factor-alpha, interleukin-6, and type 1 IFN in the airway, and increased mortality. Importantly, smoke exposure did not interfere with the development of influenza-specific memory responses; sham- and smoke-exposed animals were equally protected upon viral rechallenge.
Our study suggests that, in mice, cigarette smoke affects primary antiviral immune-inflammatory responses, whereas secondary immune protection remains intact.
研究表明，香烟烟雾会影响呼吸道宿主防御机制；然而，人们对这些烟雾诱导的变化如何影响宿主应对病原体的整体能力却知之甚少。
本研究的目的是调查主流香烟烟雾暴露对甲型流感病毒呼吸道感染后免疫炎症反应和病毒载量的影响。
将C57BL/6小鼠假暴露或烟雾暴露3至5个月，然后用2.5×10³空斑形成单位（低剂量）或2.5×10⁵空斑形成单位（高剂量）流感病毒感染。
尽管烟雾暴露减弱了气道对低剂量感染的炎症反应，但我们观察到，在高剂量流感病毒感染后，与假暴露小鼠相比，烟雾暴露小鼠的炎症增加，尽管病毒清除率相似。炎症反应增强与气道中肿瘤坏死因子-α、白细胞介素-6和1型干扰素的表达增加以及死亡率增加有关。重要的是，烟雾暴露并未干扰流感特异性记忆反应的发展；假暴露和烟雾暴露的动物在病毒再次攻击时受到同等程度的保护。
我们的研究表明，在小鼠中，香烟烟雾会影响初次抗病毒免疫炎症反应，而二次免疫保护仍然完好无损。
