Hasday J D, Bascom R, Costa J J, Fitzgerald T, Dubin W
Division of Pulmonary and Critical Care Medicine, University of Maryland Medical School, Baltimore, USA.
Chest. 1999 Mar;115(3):829-35. doi: 10.1378/chest.115.3.829.
Chronic bronchitis in cigarette smokers shares many clinical and histologic features with environmental lung diseases attributed to bacterial endotoxin (lipopolysaccharide [LPS]) inhalation. Experimental LPS inhalation mimics many of the acute effects of cigarette smoke in the lower airway. Therefore, we reasoned that LPS may be a biologically active component of cigarette smoke.
The Limulus amebocyte lysate (LAL) assay was used to measure LPS in the tobacco and filter tip components of unsmoked 1R4F experimental cigarettes and commercially available "light" cigarettes, as well as in mainstream (MS) and sidestream (SS) smoke particles generated with an automated smoking machine and collected on ventilator mainflow filters.
Blood LPS activity and plasma cytokine concentrations were measured in groups of healthy smokers and nonsmokers who reported to the walk-in clinic at the Baltimore VA Medical Center for unrelated complaints.
Blood LPS levels were measured by LAL assay and plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF receptors I and II (sTNFR I and sTNFR II) were measured by enzyme-linked immunosorbent assay.
Bioactive LPS was detected in both the tobacco portion (1R4F, 17.8+/-1.0 microg/cigarette; light, 26.8+/-7.3 microg/cigarette [mean+/-SE]) and filter tips (1R4F, 0.67+/-0.55 microg/cigarette; light, 0.70+/-0.39 microg/cigarette) of cigarettes. Bioactive LPS was also detected in both MS (1R4F, 120+/-64 ng/cigarette; light: 45.3+/-16 ng/cigarette) and SS smoke (1R4F, 18+/-1.5 ng/cigarette; light: 75+/-49 ng/cigarette). Although systemic absorption of inhaled LPS may occur, we failed to detect any differences between nonsmokers and smokers in median blood LPS levels (median values, 66.75 and 72.1 pg/mL, respectively; p = 0.55) or plasma concentrations of TNF-alpha (0 vs 0 pg/mL, respectively; p = 0.71), sTNFR I(1,469 vs 1,576 pg/mL, respectively), sTNFR II (2,011 vs 3,110 pg/mL, respectively), or IL-6 (8.8 vs 0 pg/mL, respectively; p = 0.20).
Smoking one pack of cigarettes per day delivers a dose of respirable LPS that is comparable to the levels of LPS associated with adverse health effects in cotton textile workers. Thus, we suggest that the bioactive LPS in cigarette smoke may contribute to the pathogenesis of chronic bronchitis that develops in susceptible cigarette smokers.
吸烟者的慢性支气管炎与因吸入细菌内毒素（脂多糖 [LPS]）所致的环境性肺病具有许多临床和组织学特征。实验性吸入 LPS 可模拟香烟烟雾在下呼吸道的许多急性效应。因此，我们推断 LPS 可能是香烟烟雾中的一种生物活性成分。
采用鲎试剂（LAL）测定法来测量未点燃的 1R4F 实验香烟和市售“淡味”香烟的烟草及滤嘴部分中的 LPS，以及用自动吸烟机产生并收集在通风机主流过滤器上的主流（MS）和侧流（SS）烟雾颗粒中的 LPS。
在巴尔的摩退伍军人事务医疗中心的门诊，对因无关主诉前来就诊的健康吸烟者和非吸烟者群体测量血液 LPS 活性及血浆细胞因子浓度。
通过 LAL 测定法测量血液 LPS 水平，采用酶联免疫吸附测定法测量血浆肿瘤坏死因子 -α（TNF -α）、白细胞介素 6（IL - 6）、可溶性 TNF 受体 I 和 II（sTNFR I 和 sTNFR II）的水平。
在香烟的烟草部分（1R4F，17.8±1.0 微克/支；淡味香烟，26.8±7.3 微克/支 [均值±标准误]）和滤嘴部分（1R4F，0.67±0.55 微克/支；淡味香烟，0.70±0.39 微克/支）均检测到生物活性 LPS。在 MS 烟雾（1R4F，120±64 纳克/支；淡味香烟：45.3±16 纳克/支）和 SS 烟雾（1R4F，18±1.5 纳克/支；淡味香烟：75±49 纳克/支）中也检测到生物活性 LPS。尽管吸入的 LPS 可能会发生全身吸收，但我们未检测到非吸烟者和吸烟者在血液 LPS 水平中位数（中位数分别为 66.75 和 72.1 皮克/毫升；p = 0.55）或血浆 TNF -α 浓度（分别为 0 与 0 皮克/毫升；p = 0.71）、sTNFR I（分别为 1469 与 1576 皮克/毫升）、sTNFR II（分别为 2011 与 3110 皮克/毫升）或 IL - 6（分别为 8.8 与 0 皮克/毫升；p = 0.20）方面存在任何差异。
每天吸一包香烟所吸入的可吸入性 LPS 剂量与棉纺织工人中与不良健康效应相关的 LPS 水平相当。因此，我们认为香烟烟雾中的生物活性 LPS 可能在易患慢性支气管炎的吸烟者发病机制中起作用。
