Modulation of articular chondrocyte activity by pirfenidone.
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.
Benton
Hilary P
HP
Department of VM: Anatomy, University of California, Davis, CA 95616, USA.
Esquivel
Angelica V
AV
Rice
Amber D
AD
Giri
Shri N
SN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006736:Horses; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D008070:Lipopolysaccharides; D011728:Pyridones; D009569:Nitric Oxide; C093844:pirfenidone