Thorne Peter S, Adamcakova-Dodd Andrea, Kelly Kevin M, O'neill Marsha E, Duchaine Caroline
The University of Iowa, College of Public Health, 100 Oakdale Campus, IREH Iowa City, IA 52242-5000, USA.
Am J Respir Crit Care Med. 2006 Apr 1;173(7):759-68. doi: 10.1164/rccm.200405-627OC. Epub 2005 Dec 30.
Human cases of hypersensitivity pneumonitis (HP) have been reported among machinists for over 10 yr. Although mycobacteria have been implicated as causal agents, this has not been established in experimental studies and the mechanisms remain unclear. Other constituents of in-use metalworking fluids (MWFs) may also contribute to the development of lung disease. We investigated the potential for Mycobacterium immunogenum (MI) in MWFs to induce HP.
Mice were exposed intranasally for 3 wk to MI (isolated from MWFs), Saccharopolyspora rectivirgula (positive control), saline, endotoxin, MWFs spiked with endotoxin and/or MI, used MWFs, and particulate-fortified used MWFs. Responses were assessed 96 h after the last exposure.
Mice exposed to MI in MWFs developed lung pathology consistent with HP along with significantly more monocytes and neutrophils in lung lavage, increased CD4+/CD8+ T-lymphocyte ratio, and marked pulmonary lymphocytosis on histologic examination when compared with saline-treated control mice. Mice with Grade 2 or higher pathology (0-4 point scale) exhibited significantly elevated macrophage inflammatory protein-1alpha and IL-10 and a trend toward higher RANTES 96 h after the final dose. Endotoxin coexposure augmented lung pathology.
MWFs containing mycobacteria induced granulomatous lung lesions, peribronchiolar lymphocytosis, increased cell concentrations in lavage, and up-regulation of several cytokines. These findings are consistent with HP.
在机械师中报告人类过敏性肺炎（HP）病例已有10多年。尽管分枝杆菌被认为是致病因素，但在实验研究中尚未得到证实，其机制仍不清楚。在用金属加工液（MWF）的其他成分也可能导致肺部疾病的发生。我们研究了MWF中免疫分枝杆菌（MI）诱导HP的可能性。
将小鼠经鼻暴露于MI（从MWF中分离）、直丝链孢菌（阳性对照）、生理盐水、内毒素、添加内毒素和/或MI的MWF、使用过的MWF以及颗粒强化的使用过的MWF中3周。在最后一次暴露后96小时评估反应。
与生理盐水处理的对照小鼠相比，暴露于MWF中MI的小鼠出现了与HP一致的肺部病理变化，肺灌洗中的单核细胞和中性粒细胞明显增多，CD4+/CD8+T淋巴细胞比值增加，组织学检查显示明显的肺淋巴细胞增多。病理分级为2级或更高（0-4分制）的小鼠在最后一剂后96小时巨噬细胞炎性蛋白-1α和IL-10显著升高，RANTES有升高趋势。内毒素共同暴露加剧了肺部病理变化。
含有分枝杆菌的MWF诱导了肉芽肿性肺病变、细支气管周围淋巴细胞增多、灌洗中细胞浓度增加以及几种细胞因子的上调。这些发现与HP一致。
