Cytokines, Chemokines, and Inflammation in Pulmonary Arterial Hypertension

According to the World Symposium Pulmonary Hypertension (WSPH) classification, pulmonary hypertension (PH) is classified into five categories based on etiology. Among them, Group 1 pulmonary arterial hypertension (PAH) disorders are rare but progressive and often, fatal despite multiple approved treatments. Elevated pulmonary arterial pressure in patients with WSPH Group 1 PAH is mainly caused by increased pulmonary vascular resistance (PVR), due primarily to sustained pulmonary vasoconstriction and excessive obliterative pulmonary vascular remodeling. Growing evidence indicates that inflammation plays a critical role in the development of pulmonary vascular remodeling associated with PAH. While the role of auto-immunity is unclear, infiltration of inflammatory cells in and around vascular lesions, including T- and B-cells, dendritic cells, macrophages, and mast cells have been observed in PAH patients. Serum and plasma levels of chemokines, cytokines, and autoantibodies are also increased in PAH patients; some of these circulating molecules are correlated with disease severity and survival. Preclinical experiments have reported a key role of the inflammation in PAH pathophysiology in vivo. Importantly, anti-inflammatory and immunosuppressive agents have further exhibited therapeutic effects. The present chapter reviews published experimental and clinical evidence highlighting the canonical role of inflammation in the pathogenesis of PAH and as a major target for the development of anti-inflammatory therapies in patients with PAH.