1. Anti-Fibrotic Action

Pirfenidone reduces pathological scar formation by inhibiting key profibrotic pathways:

  • Downregulates TGF-β (Transforming Growth Factor-β): TGF-β is a central cytokine in skin fibrosis and scarring. Pirfenidone inhibits its production, blocking excessive fibroblast proliferation and myofibroblast differentiation.
  • Suppresses Collagen Production: Pirfenidone significantly reduces collagen I and III expression, curbing extracellular matrix (ECM) accumulation.
  • Modulates other Growth Factors: It lowers the levels of:
      '
    • Platelet-Derived Growth Factor (PDGF)
    • Vascular endothelial growth factor (VEGF)
    • Fibroblast Growth Factor β (FGF-β)

2. Anti-Inflammatory Action

Inflammation is a precursor to fibrosis. Pirfenidone helps modulate this early response:

  • Inhibits Proinflammatory Chemokines and Cytokines, most notably tumour necrosis factor (TNF)-α, interleukin (IL)-4, IL-13, IL-1β, IL-6, IL-8, and IL-12
  • Promotes Anti-inflammatory Cytokines: Enhances IL-10 activity, which limits prolonged inflammatory cycles.

3. Antioxidant Action

Oxidative stress contributes to chronic inflammation and fibrosis.

  • Pirfenidone scavenges free radicals and decreases Reactive Oxygen Species (ROS) levels in tissue microenvironment.

Impact of Pirfenidone

Cellular Function

Effect of Pirfenidone

Fibroblast Proliferation

Reduced

Myofibroblast Differentiation

Inhibited

Collagen Synthesis

Reduced

Cytokine Expression

Reduced

Oxidative Stress

Reduced

Summary

Pirfenidone acts at multiple levels to prevent and reverse scar formation:

  • Interrupts fibrotic signaling (TGF-β, PDGF)
  • Modulates immune response
  • Reduces collagen deposition
  • Improves wound remodeling

References

  1. Knighton K, Babun A, Turney J, Evans B, Sehgal I. Pirfenidone in Skin Fibrosis and Scarring: From Bench Insights to Clinical Data. Med Sci (Basel). 2025 Aug 20;13(3):148

  2. Aimo A, Cerbai E, Bartolucci G, Adamo L, Barison A, Lo Surdo G, Biagini S, Passino C, Emdin M. Pirfenidone is a cardioprotective drug: Mechanisms of action and preclinical evidence. Pharmacol Res. 2020 May;155:104694

  3. Aimo A, Spitaleri G, Nieri D, Tavanti LM, Meschi C, Panichella G, Lupón J, Pistelli F, Carrozzi L, Bayes-Genis A, Emdin M. Pirfenidone for Idiopathic Pulmonary Fibrosis and Beyond. Card Fail Rev. 2022 Apr 14;8:e12

  4. Babariya H, Gaidhane SA, Acharya S, Kumar S. Pirfenidone as a Cornerstone in the Management of Fibrotic Interstitial Lung Diseases and Its Emerging Applications: A Comprehensive Review. Cureus. 2024 Sep 30;16(9):e70497

  5. Visner GA, Liu F, Bizargity P, Liu H, Liu K, Yang J, Wang L, Hancock WW. Pirfenidone inhibits T-cell activation, proliferation, cytokine and chemokine production, and host alloresponses. Transplantation. 2009 Aug 15;88(3):330-8

  6. Dai Z, Jiang Y, Guo H, Lu Y, Chen W, Liang T. Pirfenidone Ameliorates Hypertrophic Scar Through Inhibiting Proliferation and Migration of Fibroblasts by Regulating the Wnt/GSK-3β/β-Catenin Signaling Pathway. J Burn Care Res. 2025 Aug 30;46(4):854-861

  7. Torre A, Martínez-Sánchez FD, Narvaez-Chávez SM, Herrera-Islas MA, Aguilar Salinas CA, Córdova-Gallardo J. Pirfenidone use in fibrotic diseases: What do we know so far? Immun Inflamm Dis. 2024 Jul;12(7):e1335.