Idiopathic pulmonary fibrosis: from monocyte and macrophage inflammation to a novel, non-invasive measurement of pulmonary density

The anti-fibrotic drug nintedanib (NTD) has been approved for the management of Idiopathic Pulmonary Fibrosis (IPF), a rare progressive interstitial lung disease. Monocytes/macrophages and alveolar macrophages have been demonstrated to contribute to the wound healing process, promoting inflammation and collagen deposition. Aim: We intend to evaluate the effects of NTD on phenotype and responsiveness of monocytes/macrophages isolated from IPF patients before (TO) and after 3 months of treatment (T1) with the drug. In this thesis the results obtained from patients at TO will be showed. Samples from healthy volunteers and from patients will be challenged in vitro with NTD. Methods: Monocytes were isolated from peripheral blood and differentiated into M1 and M2 macrophages; cell viability, superoxide anion production and surface markers expression were evaluated. Results: we included 10 IPF patients and 5 healthy volunteers. For in vitro experiments, we used increasing concentrations of NTD up to the highest of 15nM. In monocytes from both healthy volunteers and patients NTD reduced the basal production of superoxide anion and at 15nM the effect was similar in both populations. After NTD treatment we observed a reduction of non classical monocytes percentage, with a relative reduction of classical monocytes. NTD did not significantly affect the basal 02- production in M1 neither in M2, but it reduced in a dose dependent manner the PMA-induced burst in both macrophage populations. Among surface markers' expression, we observed a reduction of CD206 in M2 macrophages of IPF subjects after NTD stimulation. Conclusions: Our results could build the basis to verify if in IPF patients monocyte production of oxidative stress would influence macrophages polarization, and to support the antifibrotic effects of NTB also by the reduction of CD206 profibrotic marker expression in M2 cells