Inflammation in pulmonary hypertension: what we know and what we could logically and safely target first.
Cohen-Kaminsky S, Hautefort A, Price L, Humbert M, Perros F.
Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, F-94276, France; INSERM UMR-S 999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, LabEx LERMIT, Le Plessis-Robinson, F-92350, France; Centre Chirurgical Marie Lannelongue, Département de recherche Médicale, Le Plessis-Robinson, F-92350, France.
Pulmonary Hypertension Service, Royal Brompton Hospital, SW3 6NP, UK.
Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, F-94276, France; INSERM UMR-S 999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, LabEx LERMIT, Le Plessis-Robinson, F-92350, France; Centre Chirurgical Marie Lannelongue, Département de recherche Médicale, Le Plessis-Robinson, F-92350, France; AP-HP, DHU TORINO, Centre National de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, F94270, France.
Abstract
Inflammation is important for the initiation and the maintenance of vascular remodeling in most of the animal models of pulmonary arterial hypertension (PAH), and therapeutic targeting of inflammation in these models blocks PAH development. In humans, pulmonary vascular lesions of PAH are the source of cytokine and chemokine production, related to inflammatory cell recruitment and lymphoid neogenesis. Circulating autoantibodies to endothelial cells and to fibroblasts have been reported in 10-40% of patients with idiopathic PAH, suggesting a possible role for autoimmunity in the pathogenesis of pulmonary vascular lesions. Current specific PAH treatments have immunomodulatory properties, and some studies have demonstrated a correlation between levels of circulating inflammatory mediators and patient survival. New immunopathological approaches to PAH should enable the development of innovative treatments for this severe condition.
KEYWORDS: Autoimmunity, cytokines, immunopathology, immunotherapy, inflammation, pulmonary arterial hypertension, pulmonary hypertension.
PMID:24747559