Modulation of articular chondrocyte activity by pirfenidone.
Abstract: Pirfenidone is under investigation as an anti-inflammatory and anti-fibrotic agent in several organs including lung. Since important features of arthritic conditions include inflammation and long-term damage to articular cartilage, we have investigated whether PD can suppress chondrocyte responses to bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1); modulators that induce a cascade of inflammatory responses that lead to articular joint tissue damage. PD (0 - 5microM) showed no effect on cell number or viability when incubated with high density primary equine chondrocyte cultures for a 24 hr period. PD did not stimulate nitric oxide (NO) release by chondrocytes when added alone but LPS and IL-1-induced NO release was inhibited by PD, in a dose-dependent manner. PD did not significantly influence GAG release from cartilage matrix nor did it stimulate or suppress the GAG releasing actions of LPS or IL-1. We conclude that PD is capable of attenuating the cytokine-induced production of the inflammatory mediator, NO by chondrocytes, without stimulating matrix glycosaminoglycan loss from cartilage. PD may have potential as an anti-inflammatory agent in the joint.
Publication Date: 2005-02-03 PubMed ID: 15686126
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research explores the potential of pirfenidone, a drug with anti-inflammatory properties, in suppressing the harmful effects of inflammation and tissue damage in joints – key features of arthritis. Through various tests, researchers found that pirfenidone can hinder the production of certain inflammatory compounds in joint cells, without causing harmful side effects.
Introduction
- The paper focuses on the drug pirfenidone, which is already known for its anti-inflammatory and anti-fibrotic properties when used in the treatment of certain organ diseases, primarily the lung.
- The researchers decided to explore the drug’s benefits in the context of arthritic conditions, marked by inflammation and long-term damage to articular cartilage – the smooth tissue covering the ends of bones where they meet to form joints.
Methodology
- The team investigated the effect of pirfenidone on chondrocytes – the cells found in healthy cartilage – when these cells were exposed to bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1).
- LPS and IL-1 are known to trigger inflammatory response sequences, contributing to tissue damage in the joints.
- The researchers utilized high-density primary equine chondrocyte cultures, maintained for a period of 24 hours, across varying doses of pirfenidone.
Results and Observations
- While pirfenidone had no impact on the number or viability of the chondrocyte cultures, it effectively lowered the release of nitric oxide (NO), a mediator of inflammation, induced by LPS and IL-1. This inhibitory effect of pirfenidone was found to be dose-dependent.
- The drug also didn’t significantly affect the release of glycosaminoglycan (GAG), a compound contributing to the strength and elasticity of cartilage, from the cartilage matrix. Pirfenidone neither stimulated nor hindered the actions of LPS or IL-1 toward GAG release.
Conclusion
- The research concludes that pirfenidone has the potential to limit the harmful inflammatory responses induced by LPS and IL-1 in chondrocytes. It can block the production of NO, an inflammatory mediator, without causing glycosaminoglycan loss from the cartilage.
- Consequently, the study posits that pirfenidone may carry potential as an anti-inflammatory remedy for joint conditions, particularly arthritis.
Cite This Article
APA
Benton HP, Esquivel AV, Rice AD, Giri SN.
(2005).
Modulation of articular chondrocyte activity by pirfenidone.
Res Commun Mol Pathol Pharmacol, 113-114, 275-288.
Publication
Researcher Affiliations
- Department of VM: Anatomy, University of California, Davis, CA 95616, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Cartilage, Articular / drug effects
- Cartilage, Articular / metabolism
- Cells, Cultured
- Chondrocytes / drug effects
- Chondrocytes / metabolism
- Glycosaminoglycans / metabolism
- Horses
- Lipopolysaccharides / antagonists & inhibitors
- Nitric Oxide / biosynthesis
- Nitric Oxide / metabolism
- Pyridones / pharmacology
Citations
This article has been cited 1 times.- Chan DD, Li J, Luo W, Predescu DN, Cole BJ, Plaas A. Pirfenidone reduces subchondral bone loss and fibrosis after murine knee cartilage injury.. J Orthop Res 2018 Jan;36(1):365-376.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists