Anti-inflammatory and immunosuppressive agents in PAH

Pulmonary arterial hypertension (PAH) pathobiology involves a remodeling process in distal pulmonary arteries, as well as vasoconstriction and in situ thrombosis, leading to enhanced pulmonary vascular resistance and pressure, to right heart failure and death. The exact mechanisms accounting for PAH development remain unknown, but growing evidence demonstrate that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Not surprisingly, PAH is often associated with diverse inflammatory disorders. Furthermore, pathologic specimens from PAH patients reveal an accumulation of inflammatory cells in and around vascular lesions, including macrophages, T and B cells, dendritic cells, and mast cells. Circulating levels of autoantibodies, chemokines, and cytokines are also increased in PAH patients and some of these correlate with disease severity and patients' outcome. Moreover, preclinical experiments demonstrated the key role of inflammation in PAH pathobiology. Immunosuppressive agents have also demonstrated beneficial effects in animal PAH models. In humans, observational studies suggested that immunosuppressive drugs may be effective in treating some PAH subtypes associated with marked inflammation. The present chapter reviews experimental and clinical evidence suggesting that inflammation is involved in the pathogenesis of PAH, as well the therapeutic potential of immunosuppressive agents in PAH.