Study on the mechanism of pulmonary fibrosis in rheumatic diseases.

1991 Fiscal Year Final Research Report Summary

• Project/Area Number: 01570433
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Saga Medical School
• Principal Investigator: OHTA Akihide Saga Med. Sch., Int. Med., Assist. Prof., 医学部, 講師 (40128129)
• Co-Investigator(Kenkyū-buntansha): MORITO Fumitaka Saga Med. Sch., Int. Med., Res. Edu. Assoc., 医学部, 教務員 (20157910) ; MOTOMURA Mitsuaki Saga Med. Sch., Int. Med., Assist. Prof., 医学部, 助手 (10210098)
• Project Period (FY): 1989 – 1990
• Keywords: Pulmonary fibrosis / Rheumatic diseases / Alveolar macrophage / Bronchoalveolar lavage / Collagen / Cytokines / Growth factors / Fibroblasts

Research Abstract

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.