IPF Pathogenesis: A Historical Perspective

Hematoxylin and Eosin Stains in IPF Micrograph, Zoom In

Reprinted with permission from the Annual Review of Pathology: Mechanisms of Disease, Volume 9 © 2014 by Annual Reviews www.annualreviews.org

The earliest reports of IPF-like illness date to the 19th century, including an 1872 description by German pathologist Ludwig von Buhl of a disease characterized by degeneration and desquamation of the alveolar epithelium; an infectious etiology was suspected and he termed this entity “chronic interstitial pneumonia.”1 There was little substantial progress in understanding the pathogenesis of IPF until 1969, when Liebow and Carrington summarized the histopathologic subtypes of interstitial pneumonias and suggested these differences may provide clues as to distinct pathogenic mechanisms.2 Through the 1970's and 1980's, predominant thought emphasized the role of chronic inflammation in driving IPF pathogenesis, which led to widespread use of corticosteroids and other anti-inflammatory therapies as strategies for treating IPF.3

Through the 1990's and 2000's, a more integrated model of IPF pathogenesis slowly emerged, wherein multiple factors including alveolar epithelial cells, myofibroblasts, inflammatory cells, and various mediators of “cross-talk” among these cell populations including cytokines, chemokines and extracellular matrix components interact to produce the histopathologic changes characteristic of IPF.4 Today, numerous controversies remain, including the role of genetic risk factors for IPF, the source of various fibroblast sub-populations and their respective contributions to IPF pathogenesis, and which pathways and mechanisms are most relevant as potential therapeutic targets.5

Content contributed by:
Jonathan A. Kropski, MD
Vanderbilt University