ALTERED CYTOKINE REGULATION IN THE LUNGS OF CIGARETTE SMOKERS

ALTERED CYTOKINE REGULATION IN THE LUNGS OF CIGARETTE SMOKERS
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DOI:
10.1164/ajrccm.150.3.8087340
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发表时间:
1994-09-01
影响因子:
24.7
通讯作者:
HASDAY, JD
HASDAY, JD
中科院分区:
医学1区
文献类型:
--
作者:
MCCREA, KA;ENSOR, JE;HASDAY, JD

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吸烟是导致慢性阻塞性肺疾病的主要因素,但它只发生在少数吸烟者身上。吸烟与肺部感染的易感性增加以及小气道的嗜中性粒细胞和巨噬细胞丰富的炎症有关。我们比较了9名吸烟者(19.1 ± 4.2包-年;平均值± SE)和9名非吸烟者支气管肺泡灌洗液(BALF)中肿瘤坏死因子(TNF)、白细胞介素(IL)-6和IL-8的浓度,并测定了BALF巨噬细胞体外释放TNF和IL-6的能力。与不吸烟者相比,吸烟者的BALF含有更多的细胞(65.3 +/- 13.2 vs 27.2 +/- 4.8 x 10(6); p < 0.02),但IL-6浓度低得多(1.8 +/- 1.0 vs 15.9 +/- 5.8 pg/ml; p < 0.05)。BALF细胞数量最多的两名吸烟者的BALF白细胞介素-8(IL-8)浓度升高,但两组之间的BALF IL-8浓度无差异(p = 0.08)。与来自非吸烟者的BALF巨噬细胞相比,在与脂多糖(LPS)孵育6小时期间,来自吸烟者的细胞释放较少的TNF(211 +/- 77对1,406 +/- 348单位/10(6)细胞; p < 0.01)和IL-6(5.8 +/- 2.6对64.9 +/- 23.3杂交瘤单位/ml; p < 0.02)。我们的结论是,即使在年轻,健康的吸烟者的肺微环境是显着异常,其特征是由IL-6,巨噬细胞,具有显着抑制的LPS诱导的细胞因子释放的能力,并在一些吸烟者,IL-8的浓度增加的水平降低。
Cigarette smoking is the major factor responsible for chronic obstructive lung disease, but it occurs in only a minority of smokers. Smoking is associated with increased susceptibility to pulmonary infections and with a neutrophil- and macrophage-rich inflammation of the small airways. We compared concentrations of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 in bronchoalveolar ravage fluid (BALF) and measured the capacity of BALF macrophages to release TNF and IL-6 in vitro in nine smokers (19.1 +/- 4.2 pack-years; mean +/- SE) and nine nonsmokers. Compared with nonsmokers, BALF from smokers contained more cells (65.3 +/- 13.2 versus 27.2 +/- 4.8 x 10(6); p < 0.02), but much lower concentrations of IL-6 (1.8 +/- 1.0 versus 15.9 +/- 5.8 pg/ml; p < 0.05). The two smokers with the highest number of BALF cells had increased BALF concentrations of interleukin-8 (IL-8), but there was no difference in BALF IL-8 concentrations between the two groups (p = 0.08). Compared with BALF macrophages from nonsmokers, cells from smokers released less TNF (211 +/- 77 versus 1,406 +/- 348 units per 10(6) cells; p < 0.01) and IL-6 (5.8 +/- 2.6 versus 64.9 +/- 23.3 hybridoma units per ml; p < 0.02) during a 6-h incubation with lipopolysaccharide (LPS). We conclude that even in young, healthy smokers the pulmonary microenvironment is markedly abnormal, characterized by depressed levels of IL-6, macrophages that have a markedly depressed capacity for LPS-induced cytokine release and, in some smokers, increased concentrations of IL-8.