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Original Research: PULMONARY HYPERTENSION |

Role for Interleukin-6 in COPD-Related Pulmonary Hypertension

Ari Chaouat, MD; Laurent Savale, MD; Christos Chouaid, MD; Ly Tu, BS; Benjamin Sztrymf, MD; Matthieu Canuet, MD; Bernard Maitre, MD; Bruno Housset, MD; Christian Brandt, MD; Philippe Le Corvoisier, MD; Emmanuel Weitzenblum, MD; Saadia Eddahibi, PhD; Serge Adnot, MD
Author and Funding Information

Affiliations: From the Service des Maladies Respiratoires et Réanimation Respiratoire (Dr. Chaouat), Hôpital de Brabois, Centre Hospitalier Régional Universitaire Nancy, Vandoeuvre-lès-Nancy, France; Département de Pneumologie (Drs. Chaouat, Canuet, and Weitzenblum), Nouvel Hôpital Civil, Centre Hospitalier Régional Universitaire Strasbourg, Strasbourg, France; Service de Physiologie Explorations Fonctionnelles (Drs. Savale, Sztrymf, and Adnot) and Centre d'Investigation Clinique (Dr. Le Corvoisier), Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France; Institut National de la Santé et de la Recherche Médicale U841 (Drs. Savale, Sztrymf, Maitre, Le Corvoisier, Eddahibi, and Adnot, and Mr. Tu), Faculté de Médecine de Créteil, Créteil, France; Service de Pneumologie (Dr. Chouaid), Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France; Service de Pneumologie et de Pathologie Professionnelle (Drs. Maitre and Housset), Centre Hospitalier Intercommunal de Créteil, Créteil, France; and Centre Hospitalier Régional Universitaire Strasbourg (Dr. Brandt), Hôpital Civil, Centre d'Investigation Clinique, Strasbourg, France.

Correspondence to: Ari Chaouat, MD, Centre Hospitalier Régional Universitaire de Nancy, Service des Maladies Respiratoires et Réanimation Respiratoire, Hôpital d'adultes de Brabois, Allée du Morvan, 54511 Vandoeuvre-lès-Nancy Cedex, France; e-mail: a.chaouat@chu-nancy.fr


Funding/Support: This study was supported by grants from the Institut National de la Santé et de la Recherche Médicale, Ministère de la Recherche, Institut des Maladies Rares (GIS), and Délégation à la Recherche Clinique de l'Assistance Publique-Hôpitaux de Paris. Financial support was received also from the European Commission under the sixth Framework Program (contract No. LSHM-CT-2005-018725, pulmotension).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

For editorial comment see page 658


© 2009 American College of Chest Physicians


Chest. 2009;136(3):678-687. doi:10.1378/chest.08-2420
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Background:  Pulmonary artery remodeling triggered by alveolar hypoxia is considered the main mechanism of pulmonary hypertension (PH) in COPD patients. We hypothesized that the risk for PH in COPD is increased by an elevation in the proinflammatory cytokines interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and IL-1β, as well as by specific genetic polymorphisms of these cytokines.

Methods:  We assessed cytokine plasma levels and the polymorphisms G(–174)C IL-6, C(−511)T IL-1β, and A(−2518)G MCP-1 in 148 COPD patients (recruited at two centers) with right heart catheterization data and 180 control subjects including smokers and nonsmokers. Human pulmonary artery smooth muscle cells (PA-SMCs) were cultured for IL-6 messenger RNA assays under normoxic and hypoxic conditions.

Results:  Patients with PH (mean pulmonary artery pressure [PAP], ≥ 25 mm Hg) had lower Pao2 and higher plasma IL-6 values than those without PH; there were no differences in terms of pulmonary function test results or CT scan emphysema scores. Plasma IL-6 correlated with mean PAP (r = 0.39; p < 0.001) and was included in a multiple stepwise regression analysis, with mean PAP as the dependent variable. In patients with the IL-6 GG genotype, the mean PAP value was significantly higher and PH was more common than in CG or CC patients (adjusted odds ratio, 4.32; 95% confidence interval, 1.96 to 9.54). Exposure to 4 h of hypoxia led to an about twofold increase in IL-6 messenger RNA in cultured human PA-SMCs.

Conclusions:  Inflammation, most likely involving IL-6, may contribute substantially to PH complicating COPD.

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