Study on the mechanism of pulmonary fibrosis in rheumatic diseases.

为了阐明风湿性疾病肺纤维化的机制，我们对13例风湿性疾病合并肺纤维化患者进行了支气管肺泡灌洗（BAL）研究，其中类风湿关节炎5例、硬皮病2例、多发性肌炎2例、混合性结缔组织病3例、系统性红斑狼疮1例，肺癌无肺纤维化5例作为对照组。2例类风湿关节炎患者、1例硬皮病患者、1例多发性肌炎患者和3例对照者的肺泡巨噬细胞培养上清液对人肺源性成纤维细胞系WI-38的生长有刺激作用。特别是1例多发性肌炎患者（pt-9）和1例对照（control-4）的培养上清液对WI-38的生长具有较高的刺激作用。然而，风湿性疾病合并肺纤维化组与无肺纤维化对照组的刺激作用无差异。-然后分析pt-9和control-4的肺泡巨噬细胞培养上清液对WI-38细胞胶原生成的影响。结果，两者都显示出对胶原生成的刺激作用，特别是pt-9的培养上清比对照-4的培养上清含有更高的刺激作用，这表明导致这种作用的因素可能与纤维化过程有关。进一步分析BAL上清液中tnf - α、il -1 β、IL-6和ifn - γ的水平。在风湿病组和对照组之间，这些细胞因子的水平没有差异。然而，pt-9的BAL上清显示ifn - γ水平最低。这表明低水平的ifn - γ可能与纤维化过程有关，因为ifn - γ是胶原蛋白生成的有效抑制剂，尽管其他重要因素如PDGF和TGF-B必须进一步研究。

In order to elucidate the mechanism of pulmonary fibrosis in rheumatic diseases, we performed bronchoalveolar lavage (BAL) study in 13 cases of rheumatic diseases with pulmonary fibrosis, including 5 cases of rheumatoid arthritis, 2 cases of scleroderma, 2 cases of polymyositis, 3 cases of mixed connective tissue disease, and 1 case of systemic lupus erythematosus, and in 5 cases of lung cancer without pulmonary fibrosis as a control group.The supernatant of cultured alveolar macrophages obtained from BAL from 2 cases of rheumatoid arthritis, I case of scleroderma, 1 case of polymyositis and 3 controls had a stimulatory effect on the growth of human lung-derived fibroblast line, WI-38. Especially, the culture supernatant from 1 patient with polymyositis (pt-9) and I control (control-4) contained high stimulatory effect on the growth of WI-38. However, there were no differences in the stimulatory effect between the rheumatic disease group with pulmonary fibrosis and the control group without pulmonary fibrosis. -Then, the effect of culture supernatant of alveolar macrophages from pt-9 and control-4 on the collagen production by WI-38 cells was analyzed. As a result, both showed stimulatory effect on collagen production, and especially, culture supernatant from pt-9 contained higher stimulatory effect than that from control-4, suggesting that the factor(s) responsible for this effect might be associated with the fibrotic process.Furthermore, the level of TNF-alpha, IL-1beta, IL-6, and IFN-gamma in BAL supernatant was analyzed. There were no differences in the level of these cytokines between rheumatic disease group and control group. However, BAL supernatant from pt-9 showed the lowest IFN-gamma level. This suggested that the low level of IFN-gamma might be responsible for the fibrotic process because IFN-gamma was a potent inhibitor of collagen production, although another important factors such as PDGF and TGF-B must be examined further.