Tuberc Respir Dis.  1988 Dec;35(4):229-240. 10.4046/trd.1988.35.4.229.

The Effect of Indomethacin on the Bleomycin-Induced Pulmonary Fibrosis in the Rats

• KMID: 2528582
• DOI: http://doi.org/10.4046/trd.1988.35.4.229

Abstract

The effect of indomethacin on the collagen synthesis was controversial and Thrall et al reported that indomethacin reduced the degree of pulmonary fibrosis after the bleomycin administration. According to the recent in vitro fibrobalst culture study, monocytes can produce not only stimulating factors for the fibroblasts but also the inhibitory factor(s) for the synthesis of collagen which acts by increasing the fibroblast PGE2 production. But the results of in vitro culture studies may be affected by various factors, such as the source of fibroblast, metabolic state of fibroblast,culture condition and culture methods. Furthermore, in vivo effects may be different from in vitro effects. So we performed this experiment to study the direct in vivo effect of indomethacin on the development of pulmonary fibrosis after the intratracheal injection of bleomycin and also the time sequence. The animals were divided into 4 groups: Group B received only intratracheal injection of bleomycin, Group BI received indomethacin subcutaneously (2 mg/ kg/ day) after the bleomycin, Group C received only intratracheal saline and Group 1 had indomethacin in addition to saline. Serial bronchoalveolar lavages, histopathologic examination, and the measurement of total hydroxyproline content of the lung and collagen synthesis rate of the lung tissue using ³H-proline were done on 3 days, one week , 2 weeks, 4 weeks, and 6 weeks after the bleomycin. We found: (1) Total cell counts, percentage of neutrophils and Iymphocytes were markedly increased in group B and group BI from 3 days after the bleomycin to 2 weeks. There was no significant difference in bronchoalveolar lavage fluid cell patterns and histopathologic findings between Group B and Group BI. (2) In Group B, total hydroxyproline content of the lung was increased significantly from one week (160±28.5 %) after the bleomycin. In Group BI, from 3 days after the bleomycin, the increase of hydroxyproline content was statistically significant. (3) In Group B, the incorporation rate of ³H-proline to newly synthesized collagen per specific radioactivity of free proline pool was increased to 265% of control group from the 3rd day of bleomycin injection to 2 weeks and then decreased to the level of contol group. In Goup BI, it was significantly higher than Group B (589% of control group) on day 3, but from 1 week after the bleomycin, there was no difference between Group B and BI. (4) The synthesis rate of noncollagenous protein was also enhanced from day 3 to 1 week in group B and BI without significant difference between these 2 groups. These results suggest that indomethacin stimulates the collagen synthesis in the early acute stage probably by blocking the effect of monocyte derived fibroblast suppressive factor(s).