Cyclosporin A upmodulates bleomycin-induced pulmonary fibrosis in BALB/c mice

被引:8
作者
Lossos, IS
Or, R
Ginzburg, V
Christensen, TG
Mashriki, Y
Breuer, R
机构
[1] Hadassah Univ Hosp, Inst Pulmonol, Lung Cellular & Mol Biol Lab, IL-91120 Jerusalem, Israel
[2] Hadassah Univ Hosp, Dept Bone Marrow Transplantat, IL-91120 Jerusalem, Israel
[3] Hebrew Univ Hadassah Med Sch, Jerusalem, Israel
[4] Boston Univ, Sch Med, Dept Pathol, Mallory Inst Pathol, Boston, MA USA
关键词
BALB/c mice; cyclosporin A; lung fibrosis; Th1inflammatory response; Bleomycin;
D O I
10.1159/000063273
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background. Intratracheal instillation of bleomycin (Bleo) into rodents serves as a model for human lung fibrosis. Various mouse strains respond differently to Bleo, and BALB/c mice are relatively resistant. Objective: Since T lymphocytes have been shown to play a major role in this model, the effect of the immunomodulator cyclosporin A (CyA) on lung fibrosis was studied in Bleo-'resistant' BALB/c mice. Methods: Pulmonary fibrosis was induced by a single intratracheal (IT) instillation of Bleo. One of the four following treatments was given to one of four groups of female BALB/c mice: (1) Bleo-CyA: IT Bleo and daily intraperitoneal (IP) injections of CyA 100 mg/day starting 1 day before IT instillation of Bleo; (2) Bleo-Sal:, IT Bleo and IF injections of saline; (3) Sal-CyA: IT saline and IP CyA 100 mg/kg; (4) Sal-Sal: IT and IP saline. The animals were killed on day 14. Fibrosis was evaluated by analysis of hydroxyproline and by quantitative image analysis of the fibrosis fraction. Ex vivo IFN-gamma, IL-4, IL-13 and IL-5 secretion by peribronchial lymphatic tissue lymphocytes was measured. Results: Pretreatment with CyA upmodulated Bleo-induced lung fibrosis in the Bleo-'resistant' BALB/c mice; hydroxyproline was higher in Bleo-CyA compared to Bleo-Sal animals and both hydroxyproline and fibrosis fraction measurements were higher in Bleo-CyA compared to Sal-Sal. Cytokine secretion by lymphocytes demonstrated increased IFN-gamma/IL-4 and IFN-gamma/IL-13 mean secretion ratios in the Bleo-CyA animals compared to the Bleo-Sal animals. Conclusions: These results indicate that CyA upmodulates Bleo-incluced lung fibrosis in Bleo-'resistant' BALB/c mice by allowing the emergence of a Th1 inflammatory response. Copyright (C) 2002 S. Karger AG, Basel.
引用
收藏
页码:344 / 349
页数:6
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