Growth Factors in Pleural Fibrosis

Steven E. Mutsaers; Ioannis Kalomenidis; Nicola A. Wilson; Y.C. Gary Lee

Disclosures

Curr Opin Pulm Med. 2006;12(4):251-258. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review: Pleural fibrosis is a double-edged sword in clinical settings. Successful induction of pleural fibrosis is the basis of therapeutic pleurodesis. On the other hand, pleural septations and fibrosis are undesirable outcomes in pleural infection and fibrothoraces. The significance of growth factors in the pathogenesis of pleural fibrosis has become increasingly apparent.
Recent Findings: Recent findings have indicated that transforming growth factor β is a key mediator of pleural fibrosis and demonstrated the therapeutic potential of both transforming growth factor β itself and transforming growth factor β inhibitors. Basic fibroblast growth factor has been highlighted as a key factor in successful pleurodesis, and in the formation of pleural effusions. Vascular endothelial growth factor inhibition has been shown to decrease pleural fibrosis in vivo. By contrast, hepatocyte growth factor stimulates non-fibrotic healing, while inhibition increases fibrosis.
Summary: The actions of the growth factors, and their inhibitors, are potentially and/or currently applicable in a clinical setting. Understanding the biology of these growth factors may allow therapeutic manipulation of these cytokines to create pleurodesis or to inhibit pleural (and peritoneal) adhesion/fibrosis.

Introduction

Pleural fibrosis, and resultant pleural adhesions/thickening, can be beneficial or detrimental, dependent on clinical settings. Iatrogenic induction of pleural fibrosis, in the form of pleurodesis, is commonly used to obliterate the pleural cavity for the treatment of recurrent effusion or pneumothorax. On the other hand, pleural fibrosis and adhesions are undesirable outcomes in other pleural diseases. Pleural infections affect over 65 000 patients in the USA and UK each year, with a mortality of 20%.[1] Evacuation of pleural pus is often prohibited by dense adhesions. A recent multicentre trial showed that fibrinolytics did not improve clinical outcomes in empyema, highlighting the urgency to explore novel intrapleural adjunct therapies to inhibit adhesion formation.[2] Pleural fibrosis is also an undesirable outcome in fibrothoraces, which can complicate pleuritis following asbestos exposure, tuberculosis and trauma.

The past few decades have seen the discovery of increasing numbers of growth factors, and continual uncovering of their biological behaviours. Increasing reports have demonstrated that many of these growth factors play important roles in the pleura in a wide range of disease processes, especially in pleural fibrosis, but also in pleural fluid formation, proliferation of mesothelioma, etc. A thorough mechanistic understanding of the biology of these growth factors may allow therapeutic manipulation of the process of pleural fibrosis. This article summarizes the key knowledge to date on several of the most studied growth factors.

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