Interleukin-13 in the pathogenesis of pulmonary artery hypertension

Background: Interleukin (IL)-13 is a regulatory factor of tissue remodeling and is involved in the pathogenesis of pulmonary artery hypertension (PAH). However, the implications of IL-13 in PAH remains uncertain. This article aims to describe the current knowledge on production and function of IL-13 and its receptors in the mechanisms of PAH. Content: The study materials of this article were based on comprehensive literature retrieval of publications of IL-13 in PAH. These study materials were carefully reviewed, analyzed and discussed. Summary: IL-13 levels in blood and lung tissue were elevated in both animal models of PAH and patients with PAH in comparison to non-PAH controls. Types I and II IL-13 receptors participate in pulmonary artery remodeling through signal transducer and activator of transcription (STAT) 6 or through phosphatidylinositol 3-kinase (PI3K), STAT3 and mitogen activated protein kinase (MAPK) pathways. Oxidant, arginase 2 (Arg2) and hypoxia-inducible factor 1 alpha are involved in the proliferation of pulmonary artery smooth muscle cells. Outlook: Types I and II IL-13 receptors play an important role in the IL-13 signaling by STAT6 via Janus kinase kinases, and by PI3K, STAT3 and MAPK pathways, respectively. Alternative pathways, including oxidant, Arg2 and hypoxia-inducible factor 1a might be also involved in the pathological process of PAH development. Investigational therapies by inflammatory suppression or thrombolytic and anticoagulant agents could inhibit intimal hyperplasia of the pulmonary arteries and suppress pulmonary vasculature remodeling. Drug research and development oriented by this hypothesis would confer benefits to the treatment of PAH.