Inflammatory Mechanisms in HIV-Associated Pulmonary Arterial Hypertension

Colas Tcherakian; Louis-Jean Couderc; Marc Humbert; Véronique Godot; Olivier Sitbon; Philippe Devillier

doi:10.1055/s-0033-1356489

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2013; 34(05): 645-653
DOI: 10.1055/s-0033-1356489

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inflammatory Mechanisms in HIV-Associated Pulmonary Arterial Hypertension

Colas Tcherakian

¹Service de Pneumologie, Hôpital Foch, Suresnes, France

²Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles Saint Quentin en Yvelines, France

³UPRES EA220, Hopital Foch, Université Versailles Saint Quentin en Yvelines, France

,

Louis-Jean Couderc

¹Service de Pneumologie, Hôpital Foch, Suresnes, France

²Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles Saint Quentin en Yvelines, France

³UPRES EA220, Hopital Foch, Université Versailles Saint Quentin en Yvelines, France

,

Marc Humbert

⁴Faculté de médecine, Univ. Paris-Sud, Le Kremlin-Bicêtre, France

⁵AP-HP, DHU Thorax Innovation, Service de Pneumologie, HôpitalBicêtre, Le Kremlin-Bicêtre, France

⁶INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France

,

Véronique Godot

⁷INSERM U955, LabEx «Vaccinal Research Institute», Faculté de MédecineCréteil, Université Paris EstCréteil, France

,

Olivier Sitbon

⁴Faculté de médecine, Univ. Paris-Sud, Le Kremlin-Bicêtre, France

⁵AP-HP, DHU Thorax Innovation, Service de Pneumologie, HôpitalBicêtre, Le Kremlin-Bicêtre, France

⁶INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France

,

Philippe Devillier

²Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles Saint Quentin en Yvelines, France

³UPRES EA220, Hopital Foch, Université Versailles Saint Quentin en Yvelines, France

› Institutsangaben

Abstract

Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options.

Keywords

human immunodeficiency virus - inflammation - interleukin-6 - lipopolysaccharide - pulmonary arterial hypertension

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