TY - JOUR T1 - Nintedanib prevents IL-1β-stimulated proliferation of primary human lung fibroblasts from patients with idiopathic pulmonary fibrosis or from control donors JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3501 AU - Franziska Herrmann AU - Lutz Wollin Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3501.abstract N2 - Idiopathic pulmonary fibrosis (IPF) is a progressive, severely debilitating disease with a high mortality rate. Nintedanib (BIBF 1120) is a receptor tyrosine kinase inhibitor specific for platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor. Its effect on IPF disease progression measured by lung function decline has been investigated in two replicate Phase III clinical trials (INPULSIS-1 and -2) in patients with IPF. Interleukin-1 beta (IL-1β) is a potent pro-fibrotic mediator stimulating fibroblast proliferation a hallmark of IPF.Aim: To determine the effect of nintedanib on proliferation rate of IL-1β-stimulated primary human lung fibroblasts.Methods: Primary human lung fibroblasts from patients with IPF (IPF-HPF) and from non-fibrotic control donors (HPF) were incubated with nintedanib (1 nM – 1000 nM) for 30 min. Subsequently the cells were stimulated with IL-1β and cell proliferation was assessed by BrdU assay after 72 h.Results: IL-1β induced a 4.4-fold and 3.2-fold increase in the proliferation rate of normal human lung fibroblasts and IPF fibroblasts, respectively. Nintedanib prevented the IL-1β-induced increase of fibroblast proliferation in a concentration dependent manner. At human relevant concentrations of 1x10-7.5 M nintedanib inhibited proliferation of NHLF by 48 % and IPF-HLF by 51 %.Conclusion: Our data demonstrate that nintedanib inhibits the pro-proliferative fibrotic effect of IL-1β. This may contribute to the clinically documented anti-fibrotic activity of nintedanib in patients with IPF. ER -