Pirfenidone: Molecular mechanisms and potential clinical applications in lung disease
Abstract
Pirfenidone (PFD) is a pharmacological compound with therapeutic efficacy in idiopathic pulmonary fibrosis. It has been chiefly characterized as an antifibrotic agent, although it was initially developed as an antiinflammatory compound because of its ability to diminish the accumulation of inflammatory cells and cytokines. Despite recent studies that have elucidated key mechanisms, the precise molecular activities of PFD remain incompletely understood. PFD modulates fibrogenic growth factors, thereby attenuating fibroblast proliferation, myofibroblast differentiation, collagen and fibronectin synthesis, and deposition of extracellular matrix. This effect is mediated by suppression of TGF-β1 (transforming growth factor-β1) and other growth factors. Here, we appraise the impact of PFD on TGF-β1 production and its downstream pathways. Accumulating evidence indicates that PFD also downregulates inflammatory pathways and therefore has considerable potential as a viable and innovative antiinflammatory compound. We examine the effects of PFD on inflammatory cells and the production of pro- and antiinflammatory cytokines in the lung. In this context, recent evidence that PFD can target inflammasome pathways and ensuing lung inflammation is highlighted. Finally, the antioxidant properties of PFD, such as its ability to inhibit redox reactions and regulate oxidative stress-related genes and enzymes, are detailed. In summary, this narrative review examines molecular mechanisms underpinn…
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Pirfenidone reduces TGF-β signaling and inflammatory cytokine production in different murine experimental systems.
“Consistent with this, the small molecule pirfenidone (PFD), has been shown to reduce TGF-β signaling and inflammatory cytokine production in different murine experimental systems (135–137)”
From Targeting macrophages in liver fibrosis (2026) · cites this paper as [137]
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Pirfenidone for idiopathic pulmonary fibrosis and beyond
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“…a multi-tyrosine kinase inhibitor, and pirfenidone, a pyridone that can inhibit the production of inflammatory cytokines and extracellular matrix (ECM), though the precise mechanisms are incompletely understood (Lopez-de la Mora et al., 2015; Richeldi et al., 2017; Ruwanpura et al., 2020).”
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Targeting macrophages in liver fibrosis
González del Barrio, L., Ipsen, D. H., Pfister, D. R., Hancz, D., & Scott, C. L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1835489 · Cited by 3 · see citing works
“…with this, the small molecule pirfenidone (PFD), has been shown to reduce TGF-b signaling and in fl ammatory cytokine production in different murine experimental systems (135 – 137), but its main anti-fi brotic ef fi cacy in the liver is mostly attributed to suppression of HSC activation (138, 139).”
- Authors
- Ruwanpura, S. M., Thomas, B. J., & Bardin, P. G.
- Affiliations
- Monash Medical Centre (AU)
- Corresponding author
- Ruwanpura, Saleela M.
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-04-01
- Volume
- 62
- Issue
- 4
- Pages
- 413-422
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- OpenAlex
- W3002376302
- Cited by
- 317
- References
- 7
- Citations by year
- 2026: 58 · 2025: 55 · 2024: 76 · 2023: 53 · 2022: 51 · 2021: 19 · 2020: 5
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- pirfenidone, idiopathic pulmonary fibrosis, pulmonary fibrosis, antifibrotic agents, anti-inflammatory activity, TGF-β1 signaling, myofibroblast differentiation, fibroblast proliferation, extracellular matrix deposition, cytokines, inflammasome, oxidative stress, antioxidant activity, nonsteroidal anti-inflammatory drugs
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Fibroblasts, Humans, Lung, Lung Diseases, Pyridones, Oxidative Stress, Cell Proliferation
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