Bacterial endotoxin is an active component of cigarette smoke

Background: Chronic bronchitis in cigarette smokers shares many clinical an d histologic features with environmental lung diseases attributed to bacter ial endotoxin (lipopolysaccharide [LPS]) inhalation. Experimental LPS inhal ation mimics many of the acute effects of cigarette smoke in the lower airw ay. Therefore, we reasoned that LPS may be a biologically active component of cigarette smoke. Design: The Limulus amebocyte lysate (LAL) assay was used to measure LPS in the tobacco and filter tip components of unsmoked 1R4F experimental cigare ttes and commercially available "light" cigarettes, as well as in mainstrea m (MS) and sidestream (SS) smoke particles generated with an automated smok ing machine and collected on ventilator mainflow biters. Setting and participants: Blood LPS activity and plasma cytokine concentrat ions were measured in groups of healthy smokers and nonsmokers who reported to the walk-in clinic at the Baltimore VA Medical Center for unrelated com plaints. Measurements: Blood LPS levels were measured by LAL assay and plasma level of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), soluble T NF receptors I and II (sTNFR I and sTNFR II) were measured by enzyme-linked immunosorbent assay. Results: Bioactive LPS was detected in both the tobacco portion (1R4F, 17.8 +/- 1.0 mu g/cigarette; light, 26.8 +/- 7.3 mu g/cigarette [mean +/- SE]) and filter tips (1R4F, 0.67 +/- 0.55 mu g/cigarette; light, 0.70 +/- 0.39 m u g/cigarette) of cigarettes. Bioactive LPS was also detected in both MS (1 R4F, 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 s ystemic absorption of inhaled LPS may occur, we failed to detect any differ ences between nonsmokers and smokers in median blood LPS levels (median val ues, 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 1,5 76 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). Conclusions: Smoking one pack of cigarettes per day delivers a dose of resp irable LPS that is comparable to the levels of LPS associated with adverse health effects in cotton textile workers. Thus, we suggest that the bioacti ve LPS in cigarette smoke may contribute to the pathogenesis of chronic bro nchitis that develops in susceptible cigarette smokers.