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Open AccessJournal ArticleDOI

Antifibrotic activities of pirfenidone in animal models

C.J. Schaefer, +4 more
- 01 Jun 2011 - 
- Vol. 20, Iss: 120, pp 85-97
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TLDR
The consistent antifibrotic activity of pirfenidone in a broad array of animal models provides a strong preclinical rationale for the clinical characterisation of Pirfenidones in pulmonary fibrosis and, potentially, other conditions with a significant fibrotic component.
Abstract
Pirfenidone is an orally active small molecule that has recently been evaluated in large clinical trials for the treatment of idiopathic pulmonary fibrosis, a fatal disease in which the uncontrolled deposition of extracellular matrix leads to progressive loss of lung function This review describes the activity of pirfenidone in several well-characterised animal models of fibrosis in the lung, liver, heart and kidney In these studies, treatment-related reductions in fibrosis are associated with modulation of cytokines and growth factors, with the most commonly reported effect being reduction of transforming growth factor-β The consistent antifibrotic activity of pirfenidone in a broad array of animal models provides a strong preclinical rationale for the clinical characterisation of pirfenidone in pulmonary fibrosis and, potentially, other conditions with a significant fibrotic component

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Citations
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Idiopathic pulmonary fibrosis

TL;DR: This disease has improved understanding of the mechanisms of lung fibrosis, and offers hope that similar approaches will transform the management of patients with other progressive fibrotic lung diseases.
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Getting to the Heart of the Matter: New Insights Into Cardiac Fibrosis

TL;DR: This review addresses the contribution of a complex signaling network involving transforming growth factor-β, endothelin-1, angiotensin II, CCN2 (connective tissue growth factor), and platelet-derived growth factor to cardiac fibrosis.
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Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts.

TL;DR: It is demonstrated that pirfenidone modulates HLF proliferation and TGF-β-mediated differentiation into myofibroblasts by attenuating key TGF -β-induced signaling pathways.
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Immune Mechanisms in Pulmonary Fibrosis

TL;DR: The role of immune cells (T cells, neutrophils, macrophages, and fibrocytes) and soluble mediators (cytokines and chemokines) involved in pulmonary fibrosis are discussed, pointing toward novel immune-based therapeutic strategies in the field.
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Developmental pathways in the pathogenesis of lung fibrosis.

TL;DR: Current knowledge in the field is analyzed, gained from both basic and clinical research, to provide new insights into the disease process, and potential approaches to treatment of pulmonary fibrosis.
References
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Journal ArticleDOI

American thoracic society/European respiratory society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias

TL;DR: The Diagnostic Process Is Dynamic Clinical Evaluation Radiological Evaluation Role of Surgical Lung Biopsy Unclassifiable Interstitial Pneumonia Bronchoalveolar Lavage Fluid Evaluation Idiopathic Pulmonary Fibrosis.
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Mechanisms of Hepatic Fibrogenesis

TL;DR: Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease.
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Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury.

TL;DR: Establishing the importance of the normal ECM in liver has illuminated recent attempts to develop artificial liver support by recognizing that all cellular elements and supporting structures must be reconstituted to preserve differentiated function of liver ex vivo.
Journal ArticleDOI

Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.

TL;DR: The hypothesis that idiopathic pulmonary fibrosis is a fibrotic rather than an inflammatory disease is examined, and the therapeutic implications of these findings are discussed.
Journal ArticleDOI

Incidence and Prevalence of Idiopathic Pulmonary Fibrosis

TL;DR: The results suggest that idiopathic pulmonary fibrosis is probably more common in the United States than previously reported.
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