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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
1   Service de Pneumologie, Hôpital Foch, Suresnes, France
2   Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles Saint Quentin en Yvelines, France
3   UPRES EA220, Hopital Foch, Université Versailles Saint Quentin en Yvelines, France
,
Louis-Jean Couderc
1   Service de Pneumologie, Hôpital Foch, Suresnes, France
2   Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles Saint Quentin en Yvelines, France
3   UPRES EA220, Hopital Foch, Université Versailles Saint Quentin en Yvelines, France
,
Marc Humbert
4   Faculté de médecine, Univ. Paris-Sud, Le Kremlin-Bicêtre, France
5   AP-HP, DHU Thorax Innovation, Service de Pneumologie, HôpitalBicêtre, Le Kremlin-Bicêtre, France
6   INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France
,
Véronique Godot
7   INSERM U955, LabEx «Vaccinal Research Institute», Faculté de MédecineCréteil, Université Paris EstCréteil, France
,
Olivier Sitbon
4   Faculté de médecine, Univ. Paris-Sud, Le Kremlin-Bicêtre, France
5   AP-HP, DHU Thorax Innovation, Service de Pneumologie, HôpitalBicêtre, Le Kremlin-Bicêtre, France
6   INSERM UMR-S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France
,
Philippe Devillier
2   Faculté de Médecine Paris-Ile de France-Ouest, Université Versailles Saint Quentin en Yvelines, France
3   UPRES EA220, Hopital Foch, Université Versailles Saint Quentin en Yvelines, France
› Author Affiliations
Further Information

Publication History

Publication Date:
13 September 2013 (online)

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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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