The role of inflammation in the pathogenesis of idiopathic pulmonary fibrosis

Our plain-English summary of The role of inflammation in the pathogenesis of idiopathic pulmonary fibrosis, by B.D. Bringardner, C.P. Baran, T.D. Eubank, et al (Antioxidants & Redox Signaling, 2008).

The study

• Authors: B.D. Bringardner, C.P. Baran, T.D. Eubank, C.B. Marsh
• Journal: Antioxidants & Redox Signaling
• Published: 2008;10(2):287-301
• Type of article: Review
• Cited by: 259 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The role of inflammation in idiopathic pulmonary fibrosis (IPF) is controversial. If inflammation were critical to the disease process, lung pathology would demonstrate an influx of inflammatory cells, and that the disease would respond to immunosuppression. Neither is true. The classic pathology does not display substantial inflammation, and no modulation of the immune system is effective as treatment. Recent data suggest that the pathophysiology of the disease is more a product of fibroblast dysfunction than of dysregulated inflammation. The role of inflammation in disease pathogenesis comes from pathology from atypical patients, biologic samples procured during exacerbations of the disease, and careful examination of biologic specimens from patients with stable disease. We suggest that inflammation is indeed a critical factor in IPF and propose five potential nontraditional mechanisms for the role of inflammation in the pathogenesis of IPF: the direct inflammatory hypothesis, the matrix hypothesis, the growth factor-receptor hypothesis, the plasticity hypothesis, and the vascular hypothesis. To address these, we review the literature exploring the differences in pathology, prognosis, and clinical course, as well as the role of cytokines, growth factors, and other mediators of inflammation, and last, the role of matrix and vascular supply in patients with IPF.

In plain English

This article was a review of published research on idiopathic pulmonary fibrosis (IPF), a scarring lung disease of unknown cause. It was not a new study of patients or workers. The authors noted that the typical tissue pattern of IPF does not require visible inflammation and that the disease does not respond to immunosuppression. They still argued that inflammation plays a critical role, though not in the traditional sense, and proposed five possible mechanisms: direct inflammation, matrix, growth factor–receptor, plasticity and vascular. The review also described animal models used to study lung fibrosis, including bleomycin, radiation, silica and asbestos. For asbestos, the authors described the process as macrophages swallowing deposited fibers, becoming activated and starting an inflammatory cascade. In the models they tabulated, alveolar macrophages were the predominant cell type after lung injury. The authors concluded that inflammation likely plays a role but that the mechanisms are not well characterized. They noted that no single animal model reproduces human IPF.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published literature (labelled a Forum Review); not an original study
• Who was studied: No new study population. The authors reviewed published human studies of IPF and animal (mainly mouse) models of pulmonary fibrosis.
• Exposure: IPF has no known cause. Among the experimental agents reviewed for inducing lung fibrosis in animals were bleomycin, FITC, silica, irradiation and asbestos, the last given by aerosol or into the windpipe (intratracheally). Smoking was also discussed.
• Main results:
  • The authors noted that the expected signs of an inflammation-driven disease, namely an influx of inflammatory cells and a response to immunosuppression, are not seen in IPF.
  • In the authors' account of asbestos-induced lung injury, macrophages engulf deposited fibers, become activated and start the inflammatory cascade that leads to fibrosis.
  • In the animal models tabulated, including asbestos given by aerosol or intratracheally, alveolar macrophages were the most numerous inflammatory cells recruited after lung injury, whatever the route of administration.
  • The authors cited their own earlier work reporting that macrophage colony-stimulating factor (M-CSF) is elevated in fluid washed from the lungs (BAL fluid) of patients with IPF.
  • The authors proposed five hypotheses (direct inflammation, matrix, growth factor–receptor, plasticity and vascular) for how inflammation could contribute to IPF.
• The authors' conclusion: The authors concluded that inflammation, although not in a traditional sense, plays a critical role in IPF, but that the mechanisms of involvement are not well characterized.
• Limitations the authors state:
  • No single animal model reproduces the full pathology of human IPF.
  • Many older studies are hard to interpret because of variable pathology and differing definitions and diagnosis of the disease.
  • The plasticity hypothesis has not been tested by careful studies.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Idiopathic, Pulmonary Fibrosis, Pathology, Fibroblast, Prognosis, Cytokine.

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