TY - JOUR T1 - PBI-compound, a novel first-in-class anti-fibrotic compound, reduces lung fibrosis in the bleomycin-induced lung fibrosis model: A comparative study with pirfenidone JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P683 AU - Lyne Gagnon AU - Mikaël Tremblay AU - François Sarra-Bournet AU - Liette Gervais AU - Shaun Abbott AU - Jean-Simon Duceppe AU - Boulos Zacharie AU - Christopher Penney AU - Pierre Laurin AU - Brigitte Grouix Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P683.abstract N2 - Background: The pathobiological mechanisms underlying the development of idiopathic pulmonary fibrosis (IPF) are highly complex.Aims: To compare the effect of PBI-Compound, pirfenidone, and combination of both compounds on inflammatory/fibrotic mRNA expression of key mediators (inflammation/pro-fibrotic: TGF-β, CTGF, IL 6, IL23p19; fibrotic: collagen I, fibronectin; and remodeling: SPARC, MMP-2), and on histological lesions in the bleomycin-induced lung fibrosis model.Methods: Intratracheal instillation of bleomycin was administered on day 0. Mice were treated with PBI-Compound, or pirfenidone, or combination of both compounds starting on day 7 to 21.Results: Bleomycin induced a significant increase in mRNA expression of all key mediators in the lung. PBI-Compound and combination therapy significantly decreased TGF-β, CTGF, IL-6 and IL23p19 expression in lung, while pirfenidone had no effect on CTGF. All treatments induced a significant reduction of collagen I and fibronectin expression to the control level (no bleomycin). PBI-Compound and combination therapy induced a significant reduction of SPARC while pirfenidone demonstrated no effect. PBI-Compound and pirfenidone induced a weak inhibition of MMP-2 while the combination therapy induced a significant reduction. Based on Ashcroft’s score, PBI-Compound and combination therapy demonstrated significant reduction of lung fibrosis while pirfenidone alone demonstrated weak but no significant activity at the histological level.Conclusions: PBI-Compound or combination therapy with pirfenidone may be an efficacious treatment in IPF. ER -