[Studies on the role of colchicine in bleomycin-induced pulmonary fibrosis in rats].
OBJECTIVE
It has well been known that cytokines and extracellular matrix protein (ECM) have played an important role in pulmonary fibrosis in animal model as well as in patients. The purpose of this study was to evaluate the suppressive effect of colchicine (Colc.) in bleomycin (BLM)-treated rats.


METHODS
Consecutive changes of interleukin-6(IL-6) and interleukin-8 (IL-8) released by alveolar macrophage (AM) were measured with murine B-cell hybridoma 7TD1 cells and micro membrane filter test. ECM and lipid peroxidation were observed with radioimmunoassay and biochemical assay respectively.


RESULTS
(1) Colc. significantly suppressed release of IL-6 by AM from day 7 to 28 (P < 0.05). But the level of IL-6 remained higher than that of the control. On the day 1 to 3, IL-8 released by AM markedly decreased (P < 0.01) and the peak of IL-8 secretion had not appeared. (2) Colc. had no protective effects on AM lipid peroxidation injury. (3) Colc. markedly decreased the level of fibronectin (FN) by AM on day 7, 14 (P < 0.01), as well as the level of laminin (LN) in bronchoalveolar lavage fluid (BALF) on day 7 to 28. However, the level of LN remained higher than that of control. (4) Colc. lessened the collagen deposition, and the lung hydroxyproline (HYP) content decreased on day 7, 14 and 28 (P < 0.05) compared with that of the control. (5) Colc. decreased exudation of inflammatory cells in the early response, as well as the degree of fibrosis in the late stage.


CONCLUSIONS
Lipid peroxidation of AM might be one of the mechanisms of tissue injury and of AM activation, which increases the release of cytokines (IL-6, IL-8) and deposition of extracellular matrix proteins (FN, LN). Colc. exertes somewhat inhibitory effects on the process of pulmonary fibrosis in animal model. Factors other than AM and its cytokines might also be involved in the pathogenesis of pulmonary fibrosis in experimental rats.
Jiang
L
L
Institute of Respiratory Disease, China Medical University, Shenyang 110001.
Chen
B
B
Li
Z
Z
D000818:Animals; D001761:Bleomycin; D003078:Colchicine / Q000494:pharmacology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D005353:Fibronectins; D015850:Interleukin-6; D016209:Interleukin-8; D007797:Laminin; D001761:Bleomycin; D003078:Colchicine