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The role of interleukin-6 in pulmonary and systemic manifestations in a murine model of chronic obstructive pulmonary disease

Onglets principaux

Pauwels, Nele S. Pilette, Charles [UCL] Bracke, Ken R. Maes, Tania Joos, Guy F. Brusselle, Guy G.

Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extrapulmonary manifestations including systemic inflammation and weight loss. Increased levels of interleukin-6 (IL-6) have been demonstrated in sputum and serum of COPD patients. Therefore, the authors investigated the in vivo role of IL-6 in a murine model of COPD. Wild-type (WT) and IL-6 knockout (KO) mice were exposed subacutely (4 weeks) and chronically (24 weeks) to air or cigarette smoke (CS). Subacute and chronic CS exposure significantly increased pulmonary IL-6 mRNA expression in lung tissue and IL-6 protein levels in bronchoalveolar lavage fluid of WT mice. However, CS-induced accumulation of inflammatory cells at both time points and lymphoid aggregate formation upon chronic CS exposure were independent of IL-6. Chonic CS exposure was associated with a significant failure to gain weight in both WT mice and IL-6 KO mice. Remarkably, air-exposed IL-6 KO mice have lower body weight, serum leptin levels, and adipose tissue mass compared to air-exposed WT mice. In conclusion, IL-6 is of minor importance in CS-induced pulmonary and systemic manifestations in mice, but this study confirms the role for IL-6 as regulator of body weight and body composition.

Type de document Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Année de publication 2010
Langue Anglais
Information sur le périodique "Experimental Lung Research" - Vol. 36, no. 8, p. 469-83 (2010)
Peer reviewed oui
Editeur Taylor & Francis Inc (Philadelphia)
issn 0190-2148
e-issn 1521-0499
Statut de la publication Publié
Affiliations UCL - Cliniques universitaires Saint-Luc
UCL - SSS/IREC - Institut de recherche expérimentale et clinique
MESH Subject Tobacco Smoke Pollution - adverse effects ; Smoking - adverse effects ; RNA, Messenger - metabolism ; Pulmonary Emphysema - chemically induced - genetics - metabolism ; Pulmonary Disease, Chronic Obstructive - chemically induced - genetics - metabolism ; Mice, Knockout ; Mice ; Male ; Lymphocytes - drug effects - metabolism - pathology ; Lung - drug effects - metabolism - pathology ; Leptin - genetics - metabolism ; Interleukin-6 - deficiency - genetics - metabolism ; Gene Expression - drug effects ; Disease Models, Animal ; Cytokines - genetics - metabolism ; Cell Count ; Bronchoalveolar Lavage Fluid - cytology ; Animals ; Adipose Tissue, White - drug effects - metabolism
Mots-clés COPD ; interleukin-6 ; pulmonary inflammation ; systemic inflammation
Liens
  1. Pauwels Romain A, Rabe Klaus F, Burden and clinical features of chronic obstructive pulmonary disease (COPD), 10.1016/s0140-6736(04)16855-4
  2. Rabe Klaus F., Hurd Suzanne, Anzueto Antonio, Barnes Peter J., Buist Sonia A., Calverley Peter, Fukuchi Yoshinosuke, Jenkins Christine, Rodriguez-Roisin Roberto, van Weel Chris, Zielinski Jan, Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease : GOLD Executive Summary, 10.1164/rccm.200703-456so
  3. Hogg James C., Chu Fanny, Utokaparch Soraya, Woods Ryan, Elliott W. Mark, Buzatu Liliana, Cherniack Ruben M., Rogers Robert M., Sciurba Frank C., Coxson Harvey O., Paré Peter D., The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease, 10.1056/nejmoa032158
  4. Agusti A. G. N., Systemic Effects of Chronic Obstructive Pulmonary Disease, 10.1513/pats.200504-026sr
  5. Nishimoto Norihiro, Kishimoto Tadamitsu, Interleukin 6: from bench to bedside, 10.1038/ncprheum0338
  6. Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei X F, Achong M K, IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses., 10.1172/jci1368
  7. Hirano Toshio, Yasukawa Kiyoshi, Harada Hisashi, Taga Tetsuya, Watanabe Yasuo, Matsuda Tadashi, Kashiwamura Shin-ichiro, Nakajima Koichi, Koyama Koichi, Iwamatsu Akihiro, Tsunasawa Susumu, Sakiyama Fumio, Matsui Hiroshi, Takahara Yoshiyuki, Taniguchi Tadatsugu, Kishimoto Tadamitsu, Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin, 10.1038/324073a0
  8. Maggio M., Guralnik J. M., Longo D. L., Ferrucci L., Interleukin-6 in Aging and Chronic Disease: A Magnificent Pathway, 10.1093/gerona/61.6.575
  9. Gabay Cem, 10.1186/ar1917
  10. Mohamed-Ali V., Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor- , in Vivo, 10.1210/jc.82.12.4196
  11. HEINRICH Peter C., BEHRMANN Iris, HAAN Serge, HERMANNS Heike M., MÜLLER-NEWEN Gerhard, SCHAPER Fred, Principles of interleukin (IL)-6-type cytokine signalling and its regulation, 10.1042/bj20030407
  12. Jones S. A., Directing Transition from Innate to Acquired Immunity: Defining a Role for IL-6, 10.4049/jimmunol.175.6.3463
  13. Quinton Lee J., Jones Matthew R., Robson Bryanne E., Simms Benjamin T., Whitsett Jeffrey A., Mizgerd Joseph P., Alveolar Epithelial STAT3, IL-6 Family Cytokines, and Host Defense duringEscherichia coliPneumonia, 10.1165/rcmb.2007-0365oc
  14. Bhowmik A., Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations, 10.1136/thorax.55.2.114
  15. Song W, Chin Med J (Engl ), 114, 1140 (2001)
  16. Bucchioni Enrica, Kharitonov Sergei A., Allegra Luigi, Barnes Peter J., High levels of interleukin-6 in the exhaled breath condensate of patients with COPD, 10.1016/j.rmed.2003.07.008
  17. van Durme Yannick M.T.A., Verhamme Katia M.C., Aarnoudse Albert-Jan L.H.J., Van Pottelberge Geert R., Hofman Albert, Witteman Jacqueline C.M., Joos Guy F., Brusselle Guy G., Stricker Bruno H.C., C-Reactive Protein Levels, Haplotypes, and the Risk of Incident Chronic Obstructive Pulmonary Disease, 10.1164/rccm.200810-1540oc
  18. Dahl Morten, Vestbo Jørgen, Lange Peter, Bojesen Stig E., Tybjærg-Hansen Anne, Nordestgaard Børge G., C-reactive Protein As a Predictor of Prognosis in Chronic Obstructive Pulmonary Disease, 10.1164/rccm.200605-713oc
  19. Gan W Q, Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis, 10.1136/thx.2003.019588
  20. Doz E., Noulin N., Boichot E., Guenon I., Fick L., Le Bert M., Lagente V., Ryffel B., Schnyder B., Quesniaux V. F. J., Couillin I., Cigarette Smoke-Induced Pulmonary Inflammation Is TLR4/MyD88 and IL-1R1/MyD88 Signaling Dependent, 10.4049/jimmunol.180.2.1169
  21. Kopf Manfred, Baumann Heinz, Freer Giulia, Freudenberg Marina, Lamers Marinus, Kishimoto Tadamitsu, Zinkernagel Rolf, Bluethmann Horst, Köhler Georges, Impaired immune and acute-phase responses in interleukin-6-deficient mice, 10.1038/368339a0
  22. D'hulst A. I., Time course of cigarette smoke-induced pulmonary inflammation in mice, 10.1183/09031936.05.00095204
  23. Bracke KR, Clin Exp Allergy., 37, 1467 (2007)
  24. Vermaelen Karim Y., Carro-Muino Ines, Lambrecht Bart N., Pauwels Romain A., Specific Migratory Dendritic Cells Rapidly Transport Antigen from the Airways to the Thoracic Lymph Nodes, 10.1084/jem.193.1.51
  25. Vermaelen Karim, Pauwels Romain, Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: Methodology and new insights, 10.1002/cyto.a.20064
  26. Thurlbeck WM, Am Rev Respir Dis., 95, 752 (1967)
  27. D'hulst An I, Maes Tania, Bracke Ken R, Demedts Ingel K, Tournoy Kurt G, Joos Guy F, Brusselle Guy G, Cigarette smoke-induced pulmonary emphysema in scid-mice. Is the acquired immune system required?, 10.1186/1465-9921-6-147
  28. Wigmore SJ, Am J Physiol., 273, E720 (1997)
  29. D'hulst A. I., Role of tumour necrosis factor-  receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema, 10.1183/09031936.06.00059305
  30. Cava Antonio La, Matarese Giuseppe, The weight of leptin in immunity, 10.1038/nri1350
  31. Yu M., The Role of Interleukin-6 in Pulmonary Inflammation and Injury Induced by Exposure to Environmental Air Pollutants, 10.1093/toxsci/68.2.488
  32. Demoor T., Bracke K. R., Maes T., Vandooren B., Elewaut D., Pilette C., Joos G. F., Brusselle G. G., Role of lymphotoxin-  in cigarette smoke-induced inflammation and lymphoid neogenesis, 10.1183/09031936.00101408
  33. Demoor T., Bracke K. R., Vermaelen K. Y., Dupont L., Joos G. F., Brusselle G. G., CCR7 Modulates Pulmonary and Lymph Node Inflammatory Responses in Cigarette Smoke-Exposed Mice, 10.4049/jimmunol.0902015
  34. Bao Shisan, Husband Alan J., Beagley Kenneth W., B1 B Cell Numbers and Antibodies against Phosphorylcholine and LPS Are Increased in IL-6 Gene Knockout Mice, 10.1006/cimm.1999.1579
  35. Rose-John S., Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer, 10.1189/jlb.1105674
  36. Wouters Emil F.M., Creutzberg Eva C., Schols Annemie M.W.J., Systemic Effects in COPD, 10.1378/chest.121.5_suppl.127s
  37. Sethi Sanjay, Murphy Timothy F., Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease, 10.1056/nejmra0800353
  38. Fattori E., Defective inflammatory response in interleukin 6-deficient mice, 10.1084/jem.180.4.1243
  39. Gosker Harry R., Langen Ramon C. J., Bracke Ken R., Joos Guy F., Brusselle Guy G., Steele Chad, Ward Kimberly A., Wouters Emiel F. M., Schols Annemie M. W. J., Extrapulmonary Manifestations of Chronic Obstructive Pulmonary Disease in a Mouse Model of Chronic Cigarette Smoke Exposure, 10.1165/rcmb.2008-0312oc
  40. Fäldt Jenny, Wernstedt Ingrid, Fitzgerald Sharyn M., Wallenius Kristina, Bergström Göran, Jansson John-Olov, Reduced Exercise Endurance in Interleukin-6-Deficient Mice, 10.1210/en.2003-1319
  41. Wallenius Ville, Wallenius Kristina, Ahrén Bo, Rudling Mats, Carlsten Hans, Dickson Suzanne L., Ohlsson Claes, Jansson John-Olov, Interleukin-6-deficient mice develop mature-onset obesity, 10.1038/nm0102-75
  42. Di Gregorio G. B., Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity, 10.1152/ajpendo.00189.2003
  43. Hoene M, Obes Rev., 9, 20 (2008)
  44. Hata Hiroshi, Sakaguchi Noriko, Yoshitomi Hiroyuki, Iwakura Yoichiroh, Sekikawa Kenji, Azuma Yoshiaki, Kanai Chieko, Moriizumi Eiko, Nomura Takashi, Nakamura Takashi, Sakaguchi Shimon, Distinct contribution of IL-6, TNF-α, IL-1, and IL-10 to T cell–mediated spontaneous autoimmune arthritis in mice, 10.1172/jci200421795
  45. Yamamoto M., Yoshizaki K., Kishimoto T., Ito H., IL-6 Is Required for the Development of Th1 Cell-Mediated Murine Colitis, 10.4049/jimmunol.164.9.4878
  46. Neurath M.F., Atreya R., Mudter J., Finotto S., Müllberg J., Jostock T., Wirtz S., Schütz M., Bartsch B., Holtmann M., Becker C., Strand D., Czaja J., Schlaak J. F., Lehr H.A., Autschbach F., Schürmann G., Nishimoto N., Yoshizaki K., Ito H., Kishimoto T., Galle P.R., Rose-John S., 10.1038/75068
  47. Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J, Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study, 10.1136/ard.2008.092866
  48. Ito Hiroaki, Takazoe Masakazu, Fukuda Yoshihiro, Hibi Toshifumi, Kusugami Kazuo, Andoh Akira, Matsumoto Takayuki, Yamamura Takehira, Azuma Junichi, Nishimoto Norihiro, A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease☆, 10.1053/j.gastro.2004.01.012
  49. Barnes Peter J., Emerging Pharmacotherapies for COPD, 10.1378/chest.08-1385
Référence bibliographique Pauwels, Nele S. ; Pilette, Charles ; Bracke, Ken R. ; Maes, Tania ; Joos, Guy F. ; et. al. The role of interleukin-6 in pulmonary and systemic manifestations in a murine model of chronic obstructive pulmonary disease. In: Experimental Lung Research, Vol. 36, no. 8, p. 469-83 (2010)
Permalien http://hdl.handle.net/2078.1/35014