THE PATHOGENESIS OF PULMONARY FIBROSIS - IS THERE A FIBROSIS GENE

Interstitial fibrosis is seen in the lung in response to a variety of insults, and often appears stereotypical in terms of its clinical and pathological features. However, exposure to a known aetiological facto r does not always lead to fibrosis. For example in bleomycin-induced p ulmonary fibrosis, a wide variation in response is seen both in humans and in animal models, which is not completely accounted for by known risk factors. These observations and the existence of a number of fami lial forms of lung fibrosis suggest a genetic predisposition. Current hypotheses concerning the pathogenesis of pulmonary fibrosis propose a n initial stage involving the influx of inflammatory cells into the in terstitium. These cells, together with activated resident cells are th en thought to release polypeptide mediators that stimulate the fibrobl ast proliferation and matrix protein synthesis typical of these disord ers. Genetic influences could have an important role in regulating a n umber of these events, altering the immunological response to injury o r modulating collagen metabolism in the lung. However, despite recent advances in molecular genetic techniques, there have been few human st udies to date. Most have concentrated on genetic loci with a high degr ee of polymorphism such as the human leucocyte antigen (HLA) system an d yield conflicting results. Others offer tantalising but as yet, inco mplete insights into the mechanisms involved. Defining the genetic abn ormalities underlying both the familial forms of pulmonary fibrosis an d the variations seen in response to lung injury should enhance our un derstanding of the pathogenic processes and help to focus research in this area. (C) 1997 Published by Elsevier Science Ltd.