Idiopathic pulmonary fibrosis: an epithelial/fibroblastic cross-talk disorder

Abstract

Idiopathic pulmonary fibrosis is a chronic and usually progressive lung disorder of unknown etiology. A growing body of evidence suggests that, in contrast to other interstitial lung diseases, IPF is a distinct entity in which inflammation is a secondary and non-relevant pathogenic partner. Evidence includes the presence of similar mild/moderate inflammation either in early or late disease, and the lack of response to potent anti-inflammatory therapy. Additionally, it is clear from experimental models and some human diseases that it is possible to have fibrosis without inflammation. An evolving hypothesis proposes that IPF may result from epithelial micro-injuries and abnormal wound healing.

Figure 1

Subepithelial fibroblastic foci in an IPF lung. Notice the marked changes in alveolar epithelium (hematoxylin & eosin, ×40 original magnification).

Figure 2

Hypothetical scheme of the main pathogenic events in IPF/UIP. Unknown insults provoke multiple microscopic foci of epithelial damage and stimulation. Activated alveolar epithelial cells release factors inducing fibroblast migration and proliferation and changes in cell phenotype. In the microenvironment of the lesion, myofibroblasts can induce epithelial cell apoptosis and basement membrane disruption, thus contributing to abnormal re-epithelialization and perpetuation of a vicious circle. Finally, fibroblasts/myofibroblasts secrete excessive amounts of extracellular matrix components and a disequilibrium between MMPs and TIMPs means that matrix degradation does not occur. The final result is an aberrant remodeling of the lung parenchyma.