Interstitial
pulmonary fibrosis (IPF) is
scarring of the lung caused by a variety of inhaled agents including
mineral particles, organic dusts, and
oxidant gases. The disease afflicts millions of individuals worldwide, and there are no effective therapeutic approaches. A major reason for this lack of useful treatments is that few of the molecular mechanisms of disease have been defined sufficiently to design appropriate targets for
therapy. Our laboratory has focused on the molecular mechanisms through which three selected
peptide growth factors could play a role in the development of IPF. Hundreds of
growth factors and
cytokines could be involved in the complex disease process. We are studying
platelet-derived growth factor because it is the most potent mesenchymal cell
mitogen yet described,
transforming growth factor beta because it is a powerful inducer of extracellular matrix (
scar tissue) components by mesenchymal cells, and
tumor necrosis factor alpha because it is a pleiotropic
cytokine that we and others have shown is essential for the development of IPF in animal models. This review describes some of the evidence from studies in humans, in animal models, and in vitro, that supports the
growth factor hypothesis. The use of modern molecular and transgenic technologies could elucidate those targets that will allow effective therapeutic approaches.