|Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥1,600,000 (Direct Cost: ¥1,600,000)
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.