Senthilselvan Ambikaipakan, Dosman James A, Chénard Liliane, Burch Lauranell H, Predicala Bernardo Z, Sorowski Randine, Schneberger David, Hurst Tom, Kirychuk Shelley, Gerdts Volker, Cormier Yvon, Rennie Donna C, Schwartz David A
Department of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
J Allergy Clin Immunol. 2009 May;123(5):1034-40, 1040.e1-2. doi: 10.1016/j.jaci.2009.02.019. Epub 2009 Apr 14.
Toll-like receptor 4 (TLR4) variants have been shown to reduce the respiratory responses to inhaled LPS in controlled experiments among healthy volunteers.
We sought to investigate whether naive subjects with TLR4 variants showed reduced respiratory response to a complex aerosol including endotoxin as a major constituent.
Twenty-nine nonsmoking, nonatopic healthy subjects with TLR4 299/399 polymorphisms and 29 age- and sex-matched, wild-type TLR4 control subjects were exposed for 5 hours each in a noncontaminated environment (baseline day) and in a swine confinement facility (exposure day). There were 16 men and 13 women in each of the 2 age- and sex-matched groups.
TLR4 polymorphic subjects who were exposed to high endotoxin levels (>or=1550 EU/m(3)) had less reduction in the percentage across-shift change in FEV(1) from baseline than did wild-type subjects exposed to similar endotoxin levels. Among subjects exposed to higher endotoxin levels, the mean differences in the percentage across-shift changes between baseline and exposure days were significantly less in TLR4 polymorphic subjects compared with those seen in wild-type subjects in FEV(1) (-8.48% +/- 1.52% [mean +/- SE] vs -11.46% +/- 1.79%, P = .001), forced expiratory flow between 25% and 75% of forced vital capacity (-18.30% +/- 1.99% vs -24.14% +/- 3.28%, P = .009), and FEV(1)/forced vital capacity ratio (-5.40% +/- 0.56% vs -8.53% +/- 1.51%, P = .04). These patterns were not observed in IL-6 levels from serum and nasal lavage fluid, IL-8 levels from nasal lavage fluid, white blood cell counts, or blood differential counts.
The association between TLR4 variants and reduced airway responsiveness to inhaled particulate was observed at high endotoxin concentrations, creating the possibility of certain threshold phenomena for the apparent protective effect of TLR4 variants.
在健康志愿者的对照实验中，Toll样受体4（TLR4）变体已被证明可降低对吸入脂多糖的呼吸反应。
我们试图研究携带TLR4变体的未接触过病原体的受试者对包含内毒素作为主要成分的复合气雾剂的呼吸反应是否降低。
29名具有TLR4 299/399多态性的不吸烟、非特应性健康受试者以及29名年龄和性别匹配的野生型TLR4对照受试者，分别在无污染环境（基线日）和猪舍设施（暴露日）中各暴露5小时。两个年龄和性别匹配组中每组各有16名男性和13名女性。
暴露于高内毒素水平（≥1550 EU/m³）的TLR4多态性受试者，与暴露于相似内毒素水平的野生型受试者相比，其第一秒用力呼气容积（FEV₁）自基线的跨时段变化百分比降低幅度更小。在暴露于较高内毒素水平的受试者中，TLR4多态性受试者与野生型受试者相比，基线日与暴露日之间跨时段变化百分比的平均差异在FEV₁方面显著更小（-8.48%±1.52%[平均值±标准误]对-11.46%±1.79%，P = 0.001），在用力肺活量25%至75%之间的用力呼气流量方面（-18.30%±1.99%对-24.14%±3.28%，P = 0.009），以及在FEV₁/用力肺活量比值方面（-5.40%±0.
