Anti-fibrotic drugs differently affect inflammatory and redox status in bronchial epithelial cells from Idiopathic Pulmonary Fibrosis patients

Abstract

Rationale: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease driven by continuous epithelial injuries, associated with inflammatory and profibrotic processes. While anti-fibrotic therapies (pirfenidone, nintedanib) ameliorate its course, individual responses to antifibrotics vary substantially and not all IPF patients benefit from treatment with these drugs. Aim of our study was to evaluate individual responses towards pirfenidone and nintedanib on markers of the redox and inflammatory status in bronchial epithelial cells (HBE) from IPF patients. Methods: In this pilot study, HBE cells were collected from epithelial lining fluid from IPF patients (n = 4) and controls (n = 3) by bronchoscopic microsampling. Next, HBE cells were expanded and differentiated into a bronchial epithelium in which NOX4 expression, antioxidant gene expression and pro-inflammatory cytokine secretion were evaluated in the absence or presence of pirfenidone or nintedanib. Results: NOX4 expression was slightly increased in HBE cells from IPF patients but differed on individual level. In HBE cells from patients with higher NOX4 expression, pirfenidone induced antioxidant genes whereas nintedanib decreased NOX4 expression (p = 0.07). IL-6 and IL-8 secretion was significantly increased in HBE cells derived from IPF patients compared to those from controls but were not influenced by the two drugs. Conclusion: Our results show that the cellular responses towards antifibrotics with respect to inflammatory and redox status vary substantially between individual IPF patients.