Role of IL-11 in vascular function of pulmonary fibrosis patients

Pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. Currently, no therapy can improve survival of patients diagnosed with this disease. IL-11 molecular pathway is over-expressed in proliferative disorders, however, its role in PH- associated IPF is unknown. The aim of this study was to evaluated the expression of IL-11 in IPF patients with or without PH. Also we hypothesized that the stimulation of pulmonary artery smooth muscle cells (PASMCs) and human pulmonary artery microvascular endothelial cells (HMVEC-L) with IL-11 induced the transformation into invasive myofibroblast. Human pulmonary artery rings, parenchyma tissue, broncho-alveolar lavage (BAL) and serum were obtained from control subjects (n=32), IPF (n=26) and IPF with PH patients (n=22) to study the expression and predominant distribution of IL-11 and IL-11Ra. The effect of recombinant human IL-11 on pulmonary artery remodeling was evaluated in isolated PASMCs and HMVEC-L. IL-11 and IL-11Ra were over-expressed in pulmonary arteries, parenchyma, serum and BAL of IPF patients with PH and in a lesser extend in IPF patients compared with control subjects. The inmunostaining and inmunofluorescence revealed a predominant distribution of IL11 and IL-11Rα in remodeled pulmonary arteries of IPF patients and in a greater extend in IPF with PH patients and no expression in control subject. IL-11 induced morphological changes in isolated PASMCs and HMVEC-L characterized by myofibroblast phenotype. IL-11 and IL-11Rα are over expressed in pulmonary arteries of IPF + PH patients contributing to pulmonary artery remodeling. Pharmacologic modulation of this route may be a promising target for the treatment of this disease.