Pathogenetic pathways and novel pharmaco therapeutic targets in idiopathic pulmonary fibrosis

被引:57
作者
Antomou, Katerma M.
Pataka, Athanasia
Bouros, Demosthenes
Slafakas, Nikolaos M. [1 ]
机构
[1] Univ Crete, Univ Hosp, Sch Med, Dept Thorac Med, Iraklion 71110, Crete, Greece
[2] Democritus Univ Thrace, Dept Pneumonol, Alexandroupolis, Greece
关键词
idiopathic pulmonary fibrosis treatment; pathogenesis; apoptosis; angiogenesis; oxidative stress;
D O I
10.1016/j.pupt.2006.01.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Idiopathic pulmonary fibrosis (IPF) is a poorly understood disease that Usually leads to death within 5 years of diagnosis. Despite our better understanding of IPF pathogenesis, the etiology and the precise cellular and molecular mechanisms involved are not well known. Current therapies are of unproven benefit. The aim of this review is to identify possible candidate pathways that might offer novel therapeutic targets changing the natural course of this disease. Current therapeutic approaches target at apoptosis, epithelial replacement, fibroblasts/myofibroblasts, procoagulant activity, growth factors production, angiogenesis, Th1 and Th2 cytokines and oxidative stress. Increased epithelial cells apoptosis can contribute to fibrosis, while on the other hand, decreased fibroblast or myofibroblast apoptosis promotes fibrosis. Recent findings support the notion that therapy directed at either inhibition of angiogenic or augmentation of angiostatic CXC chemokines may be a novel approach in the treatment of WE Additionally, there is little doubt that the development of novel therapeutic strategies for pulmonary fibrosis should target some profibrotic growth factors and key type 11 cytokines, such as inteleukin-13. Importantly, persistent activation of intra-alveolar procoagulant activity and subsequent abnormal fibrin turnover enhances a fibrotic response. Furthermore, increased procoagulant activity may interfere with fibrin accumulation and lack of activation of some matrix metalloproteinases responsible for an imbalance in matrix turnover. Finally. oxidative stress with increased production of oxidants in IPF is an additional mechanism proposed to explain epithelial cell apoptosis in this disease. The challenge of future targets for therapeutic intervention is to reconcile different pathogenetic pathways, and we strongly suspect that no single approach will be sufficient for a lethal disease with few therapeutic options. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:453 / 461
页数:9
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