PULMONARY FIBROSIS - CYTOKINES IN THE BALANCE

Pulmonary fibrosis can complicate diverse pulmonary and systemic patho logies. In many cases the underlying cause remains unidentified. Morta lity from the disease is increasing steadily in the UK and USA,The cli nical features are well-described, but patients frequently present at an advanced stage, and current treatments have not improved the poor p rognosis, There is a compelling need to identify the fibrotic process earlier and to develop new therapeutic agents. Increased collagen depo sition is central to the pathology and interest over the last decade h as focused on the role of cytokines in this process. These polypeptide mediators are believed to be released from both circulating inflammat ory and resident lung cells in response to endothelial and epithelial injury, Key cytokines currently implicated in the fibrotic process are transforming growth factor-beta, tumour necrosis factor-alpha and end othelin-l. This article outlines the evidence implicating these mediat ors in the pathogenesis of pulmonary fibrosis and also considers the p ossible role of cytokines with antifibrotic effects, such as interfero n-gamma, The ''balance'' of positively and negatively regulating cytok ines is discussed, and the potential for interaction with other factor s including viruses, hormones and altered antioxidant status is also c onsidered, Finally potential novel therapeutic approaches are discusse d, together with suggestions for future studies and clinical trials. A s the outcomes of different avenues of research over the last ten year s are brought together, it is clear that there is now a hitherto unriv alled opportunity to begin to tackle the treatment of this devastating disease.