Piguet P F, Collart M A, Grau G E, Kapanci Y, Vassalli P
Department of Pathology, University of Geneva, Switzerland.
J Exp Med. 1989 Sep 1;170(3):655-63. doi: 10.1084/jem.170.3.655.
The role of TNF-alpha/cachectin in the pneumopathy elicited by bleomycin has been investigated. After a single intratracheal bleomycin instillation, an increase of the lung TNF-alpha mRNA level was evident, from days 5 to 15, as shown by Northern gel analysis of whole lung RNA. In contrast, lung IL-1-alpha and GM-CSF mRNA were not detectable. In mice passively immunized with rabbit anti-mouse TNF-alpha IgG, the bleomycin-induced collagen deposition, evaluated by the total lung hydroxyproline assay on day 15, was prevented. Depletion of the CD4 and CD8 T lymphocytes by an in vivo treatment with mAb prevented the bleomycin-induced increase of TNF mRNA level and fibrosis. After an administration of bleomycin in continuous intraperitoneal perfusion, the diffuse alveolar damage observed by light and electron microscopy was almost completely prevented by anti-TNF antibody. These results indicate that in response to bleomycin, the T lymphocytes induce, by an undefined mechanism, an increase of the pulmonary TNF production, which leads to alveolar damage, growth of fibroblast, and collagen deposition.
肿瘤坏死因子-α/消瘦素在博来霉素引发的肺病中的作用已得到研究。单次气管内注入博来霉素后，如通过对全肺RNA进行Northern凝胶分析所示，从第5天到第15天，肺肿瘤坏死因子-α mRNA水平明显升高。相比之下，肺白细胞介素-1-α和粒细胞-巨噬细胞集落刺激因子mRNA无法检测到。在用兔抗小鼠肿瘤坏死因子-α免疫球蛋白被动免疫的小鼠中，通过第15天的全肺羟脯氨酸测定评估，博来霉素诱导的胶原沉积得到了预防。通过用单克隆抗体进行体内治疗使CD4和CD8 T淋巴细胞耗竭，可预防博来霉素诱导的肿瘤坏死因子mRNA水平升高和纤维化。在持续腹腔内灌注博来霉素后，光镜和电镜观察到的弥漫性肺泡损伤几乎完全被抗肿瘤坏死因子抗体预防。这些结果表明，对博来霉素的反应中，T淋巴细胞通过一种不明机制诱导肺肿瘤坏死因子产生增加，这导致肺泡损伤、成纤维细胞生长和胶原沉积。
