PMID- 19349390 OWN - NLM STAT- MEDLINE DCOM- 20091008 LR - 20220321 IS - 1931-3543 (Electronic) IS - 0012-3692 (Linking) VI - 136 IP - 3 DP - 2009 Sep TI - Role for interleukin-6 in COPD-related pulmonary hypertension. PG - 678-687 LID - S0012-3692(09)60534-1 [pii] LID - 10.1378/chest.08-2420 [doi] AB - 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-1beta, 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-1beta, 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], >or= 25 mm Hg) had lower Pao(2) 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. FAU - Chaouat, Ari AU - Chaouat A AD - Service des Maladies Respiratoires et Reanimation Respiratoire, Hopital de Brabois, Centre Hospitalier Regional Universitaire Nancy, Vandoeuvre-les-Nancy, France; Departement de Pneumologie, Nouvel Hopital Civil, Centre Hospitalier Regional Universitaire Strasbourg, Strasbourg, France. Electronic address: a.chaouat@chu-nancy.fr. FAU - Savale, Laurent AU - Savale L AD - Service de Physiologie Explorations Fonctionnelles, Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France; Institut National de la Sante et de la Recherche Medicale U841, Faculte de Medecine de Creteil, Creteil, France. FAU - Chouaid, Christos AU - Chouaid C AD - Service de Pneumologie, Hopital Saint Antoine, Assistance Publique-Hopitaux de Paris, Paris, France. FAU - Tu, Ly AU - Tu L AD - Institut National de la Sante et de la Recherche Medicale U841, Faculte de Medecine de Creteil, Creteil, France. FAU - Sztrymf, Benjamin AU - Sztrymf B AD - Service de Physiologie Explorations Fonctionnelles, Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France; Institut National de la Sante et de la Recherche Medicale U841, Faculte de Medecine de Creteil, Creteil, France. FAU - Canuet, Matthieu AU - Canuet M AD - Departement de Pneumologie, Nouvel Hopital Civil, Centre Hospitalier Regional Universitaire Strasbourg, Strasbourg, France. FAU - Maitre, Bernard AU - Maitre B AD - Institut National de la Sante et de la Recherche Medicale U841, Faculte de Medecine de Creteil, Creteil, France; Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal de Creteil, Creteil, France. FAU - Housset, Bruno AU - Housset B AD - Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal de Creteil, Creteil, France. FAU - Brandt, Christian AU - Brandt C AD - Centre Hospitalier Regional Universitaire Strasbourg, Hopital Civil, Centre d'Investigation Clinique, Strasbourg, France. FAU - Le Corvoisier, Philippe AU - Le Corvoisier P AD - Centre d'Investigation Clinique, Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France; Institut National de la Sante et de la Recherche Medicale U841, Faculte de Medecine de Creteil, Creteil, France. FAU - Weitzenblum, Emmanuel AU - Weitzenblum E AD - Departement de Pneumologie, Nouvel Hopital Civil, Centre Hospitalier Regional Universitaire Strasbourg, Strasbourg, France. FAU - Eddahibi, Saadia AU - Eddahibi S AD - Institut National de la Sante et de la Recherche Medicale U841, Faculte de Medecine de Creteil, Creteil, France. FAU - Adnot, Serge AU - Adnot S AD - Service de Physiologie Explorations Fonctionnelles, Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France; Institut National de la Sante et de la Recherche Medicale U841, Faculte de Medecine de Creteil, Creteil, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090406 PL - United States TA - Chest JT - Chest JID - 0231335 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) SB - IM CIN - Chest. 2009 Sep;136(3):658-9. PMID: 19736185 CIN - Chest. 2010 May;137(5):1250-1; author reply 1251. PMID: 20442132 MH - Adult MH - Aged MH - Case-Control Studies MH - Chemokine CCL2/blood/genetics MH - Chi-Square Distribution MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Expression MH - Genotype MH - Humans MH - Hypertension, Pulmonary/*blood/*etiology/genetics MH - Interleukin-1beta/blood/genetics MH - Interleukin-6/*blood/genetics MH - Male MH - Middle Aged MH - Polymorphism, Genetic MH - Pulmonary Disease, Chronic Obstructive/*complications/genetics MH - Regression Analysis MH - Respiratory Function Tests MH - Statistics, Nonparametric EDAT- 2009/04/08 09:00 MHDA- 2009/10/09 06:00 CRDT- 2009/04/08 09:00 PHST- 2009/04/08 09:00 [entrez] PHST- 2009/04/08 09:00 [pubmed] PHST- 2009/10/09 06:00 [medline] AID - S0012-3692(09)60534-1 [pii] AID - 10.1378/chest.08-2420 [doi] PST - ppublish SO - Chest. 2009 Sep;136(3):678-687. doi: 10.1378/chest.08-2420. Epub 2009 Apr 6.