Study on the mechanism of pulmonary fibrosis in rheumatic diseases.

为探讨风湿性疾病肺纤维化的发生机制，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，其中类风湿性关节炎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。2例类风湿性关节炎、1例硬皮病、1例多发性肌炎和3例正常人的肺泡巨噬细胞培养上清对人肺成纤维细胞株的生长有促进作用，WI-38特别是，来自1名患有多发性肌炎的患者（pt-9）和1名对照（对照-4）的培养上清液含有对WI-38生长的高刺激作用。然而，在风湿性疾病伴肺纤维化组和对照组之间的刺激作用没有差异。- 然后，分析来自pt-9和对照-4的肺泡巨噬细胞的培养上清液对WI-38细胞的胶原产生的影响。结果表明，两种细胞均能刺激胶原蛋白的生成，尤其是pt-9细胞培养上清对胶原蛋白的生成的刺激作用强于对照4细胞，提示该作用可能与纤维化过程有关。风湿性疾病组与对照组之间上述细胞因子水平无差异。然而，来自pt-9的BAL上清液显示最低的IFN-γ水平。这表明低水平的IFN-γ可能是纤维化过程的原因，因为IFN-γ是胶原蛋白产生的有效抑制剂，尽管必须进一步检查其他重要因素如PDGF和TGF-β。

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.