Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro
Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro
复制标题
DOI：
10.1164/rccm.200210-1154oc
复制
发表时间：
2004-04-15
影响因子：
24.7
通讯作者：
Cormier, Y
中科院分区：
文献类型：
--
作者：
Blanchet, MR;Israël-Assayag, E;Cormier, Y
过敏性肺炎（HP）的发生率在吸烟者中低于非吸烟者。由于尼古丁具有免疫抑制作用，我们假设它可能对体内HP诱导具有保护作用。在接受尼古丁腹腔内（IP）（0.5 - 2.0 mg/kg/天）或鼻内（IN）（0.025 - 2.0 mg/kg/天）给药的小鼠中诱导HP。IP和IN给药动物的支气管肺泡灌洗液总细胞和淋巴细胞减少，肺组织炎症减少。在2.0 mg/kg IN处理的动物的肺组织中，IFN-γ而非白细胞介素-10 mRNA表达降低。为了测试尼古丁对肺泡巨噬细胞的影响，用尼古丁处理AMJ 2-C11细胞，并用脂多糖或HP的病原体直枝多孢菌（Staphylopolyspora rectivirgula）刺激。尼古丁减少了刺激后肿瘤坏死因子的释放和肿瘤坏死因子、白细胞介素-10和IFN-γ mRNA的表达，并使脂多糖刺激的细胞中CD 80的表达降低了55%，使S. rectivirgula刺激的细胞。我们的结论是，尼古丁可能是，至少部分，负责保护吸烟者对HP。尼古丁对肺泡巨噬细胞的抑制作用可能是其作用机制之一。
The incidence of hypersensitivity pneumonitis (HP) is lower in smokers than in nonsmokers. Because nicotine is immunosuppressive, we hypothesized that it could have a protective effect on HP induction in vivo. HP was induced in mice that were treated with nicotine either intraperitoneally (IP) (0.5 to 2.0 mg/kg/day) or intranasally (IN) (0.025 to 2.0 mg/kg/day). Both IP- and IN-treated animals had fewer bronchoalveolar lavage total cells and lymphocytes and a decreased lung tissue inflammation. IFN-gamma but not interleukin-10 mRNA expression was reduced in lung tissue of 2.0-mg/kg IN-treated animals. To test the effect of nicotine on alveolar macrophages, AMJ2-C11 cells were treated with nicotine and stimulated with lipopolysaccharide or Saccharopolyspora rectivirgula, a causative agent of HP. Nicotine reduced tumor necrosis factor release and tumor necrosis factor, interleukin-10, and IFN-gamma mRNA expression after stimulation and decreased CD80 expression by 55% in lipopolysaccharide-stimulated cells and by 41% in S. rectivirgula-stimulated cells. We conclude that nicotine could be, at least in part, responsible for the protection observed in smokers against HP. The inhibitory effect of nicotine on alveolar macrophages could be one of the mechanisms involved.