Eosinophilic inflammation and worsening of lung function upon pirfenidone treatment in Fra-2 transgenic mice

Pulmonary involvement is the main cause of mortality among systemic sclerosis patients and there is an urgent need for effective therapy options. Pirfenidone is an anti-fibrotic agent approved for therapy of idiopathic pulmonary fibrosis. We tested the effects of pirfenidone in an animal model of systemic sclerosis – the Fra-2 transgenic mouse. Ectopic overexpression of Fos-related antigen-2 (Fra-2), a member of the activator protein 1 family of transcription factors, leads to vascular and interstitial pulmonary remodeling, resembling pulmonary manifestations in systemic sclerosis. Nine wild-type and 13 transgenic mice received either standard diet or pirfenidone-supplemented diet (0.28%) for 10 weeks. Compared to wild-type littermate controls, transgenic mice had reduced inspiratory capacity (-9%, p=0.130) and compliance (-18%, p=0.106), whereas tissue and airway resistance were increased (+69%, p