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Published in: Respiratory Research 1/2014

Open Access 01-12-2014 | Research

Compartment differences of inflammatory activity in chronic obstructive pulmonary disease

Authors: Jie Ji, Ida von Schéele, Jan Bergström, Bo Billing, Barbro Dahlén, Ann-Sofie Lantz, Kjell Larsson, Lena Palmberg

Published in: Respiratory Research | Issue 1/2014

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Abstract

Background

Chronic obstructive pulmonary disease (COPD) is associated with local and systemic inflammation. The knowledge of interaction and co-variation of the inflammatory responses in different compartments is meagre.

Method

Healthy controls (n = 23), smokers with (n = 28) and without (n = 29) COPD performed spirometry and dental examinations. Saliva, induced sputum, bronchoalveolar lavage (BAL) fluid and serum were collected. Inflammatory markers were assessed in all compartments using ELISA, flow cytometry and RT-PCR.

Results

Negative correlations between lung function and saliva IL-8 and matrix metalloproteinase-9 (MMP-9) were found in smokers with COPD. IL-8 and MMP-9 in saliva correlated positively with periodontal disease as assessed by gingival bleeding in non-smokers.
Tumor necrosis factor-α (TNF-α) in saliva, serum and TNF-α mRNA expression on macrophages in BAL-fluid were lower in smokers than in non-smokers. There were positive correlations between soluble TNF-α receptor 1 (sTNFR1) and soluble TNF-α receptor 2 (sTNFR2) in sputum, BAL-fluid and serum in all groups. Sputum interleukin-8 (IL-8) or interleukin-6 (IL-6) was positively correlated with sTNFR1 or sTNFR2 in non-smokers and with sTNFR2 in COPD.

Conclusion

Saliva which is convenient to collect and analyse, may be suitable for biomarker assessment of disease activity in COPD. An attenuated TNF-α expression was demonstrated by both protein and mRNA analyses in different compartments suggesting that TNF-α response is altered in moderate and severe COPD. Shedding of TNFR1 or TNFR2 is similarly regulated irrespective of airflow limitation.
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Literature
1.
go back to reference Agusti A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, Vestbo J, Lomas DA, Calverley PM, Wouters E, Crim C, Yates JC, Silverman EK, Coxson HO, Bakke P, Mayer RJ, Celli B: Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One. 2012, 7 (5): e37483-10.1371/journal.pone.0037483.PubMedPubMedCentralCrossRef Agusti A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, Vestbo J, Lomas DA, Calverley PM, Wouters E, Crim C, Yates JC, Silverman EK, Coxson HO, Bakke P, Mayer RJ, Celli B: Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One. 2012, 7 (5): e37483-10.1371/journal.pone.0037483.PubMedPubMedCentralCrossRef
2.
go back to reference Thomsen M, Ingebrigtsen TS, Marott JL, Dahl M, Lange P, Vestbo J, Nordestgaard BG: Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. JAMA. 2013, 309 (22): 2353-2361. 10.1001/jama.2013.5732.PubMedCrossRef Thomsen M, Ingebrigtsen TS, Marott JL, Dahl M, Lange P, Vestbo J, Nordestgaard BG: Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. JAMA. 2013, 309 (22): 2353-2361. 10.1001/jama.2013.5732.PubMedCrossRef
3.
go back to reference Keatings VM, Collins PD, Scott DM, Barnes PJ: Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996, 153 (2): 530-534. 10.1164/ajrccm.153.2.8564092.PubMedCrossRef Keatings VM, Collins PD, Scott DM, Barnes PJ: Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996, 153 (2): 530-534. 10.1164/ajrccm.153.2.8564092.PubMedCrossRef
4.
go back to reference He ZH, Chen Y, Chen P, Wu GB, Cai S: Local inflammation occurs before systemic inflammation in patients with COPD. Respirology. 2010, 15 (3): 478-484. 10.1111/j.1440-1843.2010.01709.x.PubMedCrossRef He ZH, Chen Y, Chen P, Wu GB, Cai S: Local inflammation occurs before systemic inflammation in patients with COPD. Respirology. 2010, 15 (3): 478-484. 10.1111/j.1440-1843.2010.01709.x.PubMedCrossRef
5.
go back to reference Lim S, Roche N, Oliver BG, Mattos W, Barnes PJ, Chung KF: Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers. regulation by interleukin-10. Am J Respir Crit Care Med. 2000, 162: 1355-1360. 10.1164/ajrccm.162.4.9910097.PubMedCrossRef Lim S, Roche N, Oliver BG, Mattos W, Barnes PJ, Chung KF: Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers. regulation by interleukin-10. Am J Respir Crit Care Med. 2000, 162: 1355-1360. 10.1164/ajrccm.162.4.9910097.PubMedCrossRef
6.
go back to reference Tartaglia LA, Goeddel DV: Two TNF receptors. Immunol Today. 1992, 13 (5): 151-153. 10.1016/0167-5699(92)90116-O.PubMedCrossRef Tartaglia LA, Goeddel DV: Two TNF receptors. Immunol Today. 1992, 13 (5): 151-153. 10.1016/0167-5699(92)90116-O.PubMedCrossRef
7.
go back to reference Vernooy JH, Kucukaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, Wouters EF: Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med. 2002, 166 (9): 1218-1224. 10.1164/rccm.2202023.PubMedCrossRef Vernooy JH, Kucukaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, Wouters EF: Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med. 2002, 166 (9): 1218-1224. 10.1164/rccm.2202023.PubMedCrossRef
8.
go back to reference Churg A, Zhou S, Wright JL: Series “matrix metalloproteinases in lung health and disease”: matrix metalloproteinases in COPD. Eur Respir J. 2012, 39 (1): 197-209. 10.1183/09031936.00121611.PubMedCrossRef Churg A, Zhou S, Wright JL: Series “matrix metalloproteinases in lung health and disease”: matrix metalloproteinases in COPD. Eur Respir J. 2012, 39 (1): 197-209. 10.1183/09031936.00121611.PubMedCrossRef
9.
go back to reference Bergstrom J: Tobacco smoking and chronic destructive periodontal disease. Odontology. 2004, 92 (1): 1-8. 10.1007/s10266-004-0043-4.PubMedCrossRef Bergstrom J: Tobacco smoking and chronic destructive periodontal disease. Odontology. 2004, 92 (1): 1-8. 10.1007/s10266-004-0043-4.PubMedCrossRef
10.
go back to reference Si Y, Fan H, Song YQ, Zhou X, Zhang J, Wang ZM: Association between periodontitis and chronic obstructive pulmonary disease in a Chinese population. J Periodontol. 2012, 83 (10): 1288-1296. 10.1902/jop.2012.110472.PubMedCrossRef Si Y, Fan H, Song YQ, Zhou X, Zhang J, Wang ZM: Association between periodontitis and chronic obstructive pulmonary disease in a Chinese population. J Periodontol. 2012, 83 (10): 1288-1296. 10.1902/jop.2012.110472.PubMedCrossRef
11.
go back to reference Bergstrom J, Cederlund K, Dahlen B, Lantz AS, Skedinger M, Palmberg L, Sundblad BM, Larsson K: Dental health in smokers with and without COPD. Plos One. 2013, 8 (3): e59492-10.1371/journal.pone.0059492.PubMedPubMedCentralCrossRef Bergstrom J, Cederlund K, Dahlen B, Lantz AS, Skedinger M, Palmberg L, Sundblad BM, Larsson K: Dental health in smokers with and without COPD. Plos One. 2013, 8 (3): e59492-10.1371/journal.pone.0059492.PubMedPubMedCentralCrossRef
12.
go back to reference Strandberg K, Ek A, Palmberg L, Larsson K: Fluticasone and ibuprofen do not add to the effect of salmeterol on organic dust-induced airway inflammation and bronchial hyper-responsiveness. J Intern Med. 2008, 264 (1): 83-94. 10.1111/j.1365-2796.2008.01928.x.PubMedCrossRef Strandberg K, Ek A, Palmberg L, Larsson K: Fluticasone and ibuprofen do not add to the effect of salmeterol on organic dust-induced airway inflammation and bronchial hyper-responsiveness. J Intern Med. 2008, 264 (1): 83-94. 10.1111/j.1365-2796.2008.01928.x.PubMedCrossRef
13.
go back to reference von Scheele I, Larsson K, Dahlen B, Billing B, Skedinger M, Lantz AS, Palmberg L: Toll-like receptor expression in smokers with and without COPD. Resp Med. 2011, 105 (8): 1222-1230. 10.1016/j.rmed.2011.02.012.CrossRef von Scheele I, Larsson K, Dahlen B, Billing B, Skedinger M, Lantz AS, Palmberg L: Toll-like receptor expression in smokers with and without COPD. Resp Med. 2011, 105 (8): 1222-1230. 10.1016/j.rmed.2011.02.012.CrossRef
14.
go back to reference Larsson BM, Palmberg L, Malmberg PO, Larsson K: Effect of exposure to swine dust on levels of IL-8 in airway lavage fluid. Thorax. 1997, 52 (7): 638-642. 10.1136/thx.52.7.638.PubMedPubMedCentralCrossRef Larsson BM, Palmberg L, Malmberg PO, Larsson K: Effect of exposure to swine dust on levels of IL-8 in airway lavage fluid. Thorax. 1997, 52 (7): 638-642. 10.1136/thx.52.7.638.PubMedPubMedCentralCrossRef
15.
go back to reference Larsson K, Tornling G, Gavhed D, Muller-Suur C, Palmberg L: Inhalation of cold air increases the number of inflammatory cells in the lungs in healthy subjects. Eur Respir J. 1998, 12 (4): 825-830. 10.1183/09031936.98.12040825.PubMedCrossRef Larsson K, Tornling G, Gavhed D, Muller-Suur C, Palmberg L: Inhalation of cold air increases the number of inflammatory cells in the lungs in healthy subjects. Eur Respir J. 1998, 12 (4): 825-830. 10.1183/09031936.98.12040825.PubMedCrossRef
16.
go back to reference Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P, Calverley PMA, Celli B, Coxson HO, Crim C, Lomas DA, MacNee W, Miller BE, Silverman EK, Tal-Singer R, Wouters E, Rennard SI: Changes in forced expiratory volume in 1 second overtime in COPD. New Engl J Med. 2011, 365 (13): 1184-1192. 10.1056/NEJMoa1105482.PubMedCrossRef Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P, Calverley PMA, Celli B, Coxson HO, Crim C, Lomas DA, MacNee W, Miller BE, Silverman EK, Tal-Singer R, Wouters E, Rennard SI: Changes in forced expiratory volume in 1 second overtime in COPD. New Engl J Med. 2011, 365 (13): 1184-1192. 10.1056/NEJMoa1105482.PubMedCrossRef
17.
go back to reference Berenson CS, Wrona CT, Grove LJ, Maloney J, Garlipp MA, Wallace PK, Stewart CC, Sethi S: Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease. Am J Respir Crit Care Med. 2006, 174 (1): 31-40. 10.1164/rccm.200509-1461OC.PubMedPubMedCentralCrossRef Berenson CS, Wrona CT, Grove LJ, Maloney J, Garlipp MA, Wallace PK, Stewart CC, Sethi S: Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease. Am J Respir Crit Care Med. 2006, 174 (1): 31-40. 10.1164/rccm.200509-1461OC.PubMedPubMedCentralCrossRef
18.
go back to reference Chen H, Cowan MJ, Hasday JD, Vogel SN, Medvedev AE: Tobacco smoking inhibits expression of proinflammatory cytokines and activation of IL-1R-associated kinase, p38, and NF-kappaB in alveolar macrophages stimulated with TLR2 and TLR4 agonists. J Immunol. 2007, 179 (9): 6097-6106. 10.4049/jimmunol.179.9.6097.PubMedCrossRef Chen H, Cowan MJ, Hasday JD, Vogel SN, Medvedev AE: Tobacco smoking inhibits expression of proinflammatory cytokines and activation of IL-1R-associated kinase, p38, and NF-kappaB in alveolar macrophages stimulated with TLR2 and TLR4 agonists. J Immunol. 2007, 179 (9): 6097-6106. 10.4049/jimmunol.179.9.6097.PubMedCrossRef
19.
go back to reference Birrell MA, Wong S, Catley MC, Belvisi MG: Impact of tobacco-smoke on key signaling pathways in the innate immune response in lung macrophages. J Cell Physiol. 2008, 214 (1): 27-37. 10.1002/jcp.21158.PubMedCrossRef Birrell MA, Wong S, Catley MC, Belvisi MG: Impact of tobacco-smoke on key signaling pathways in the innate immune response in lung macrophages. J Cell Physiol. 2008, 214 (1): 27-37. 10.1002/jcp.21158.PubMedCrossRef
20.
go back to reference Pinto-Plata V, Casanova C, Mullerova H, de Torres JP, Corado H, Varo N, Cordoba E, Zeineldine S, Paz H, Baz R, Cortopassi F, Celli BR: Inflammatory and repair serum biomarker pattern association to clinical outcomes in COPD. Respir Res. 2012, 13: 71-10.1186/1465-9921-13-71.PubMedPubMedCentralCrossRef Pinto-Plata V, Casanova C, Mullerova H, de Torres JP, Corado H, Varo N, Cordoba E, Zeineldine S, Paz H, Baz R, Cortopassi F, Celli BR: Inflammatory and repair serum biomarker pattern association to clinical outcomes in COPD. Respir Res. 2012, 13: 71-10.1186/1465-9921-13-71.PubMedPubMedCentralCrossRef
21.
go back to reference Standardization of spirometry, 1994 update. Am J Respir Crit Care Med. 1995, 152 (3): 1107-1136. 10.1164/ajrccm.152.3.7663792. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med. 1995, 152 (3): 1107-1136. 10.1164/ajrccm.152.3.7663792.
22.
go back to reference Di Francia M, Barbier D, Mege JL, Orehek J: Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1994, 150 (5 Pt 1): 1453-1455. 10.1164/ajrccm.150.5.7952575.PubMedCrossRef Di Francia M, Barbier D, Mege JL, Orehek J: Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1994, 150 (5 Pt 1): 1453-1455. 10.1164/ajrccm.150.5.7952575.PubMedCrossRef
23.
go back to reference van der Vaart H, Koeter GH, Postma DS, Kauffman HF, ten Hacken NH: First study of infliximab treatment in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005, 172 (4): 465-469. 10.1164/rccm.200501-147OC.PubMedCrossRef van der Vaart H, Koeter GH, Postma DS, Kauffman HF, ten Hacken NH: First study of infliximab treatment in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005, 172 (4): 465-469. 10.1164/rccm.200501-147OC.PubMedCrossRef
24.
go back to reference Dentener MA, Creutzberg EC, Pennings HJ, Rijkers GT, Mercken E, Wouters EF: Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease: a pilot study. Respiration. 2008, 76 (3): 275-282. 10.1159/000117386.PubMedCrossRef Dentener MA, Creutzberg EC, Pennings HJ, Rijkers GT, Mercken E, Wouters EF: Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease: a pilot study. Respiration. 2008, 76 (3): 275-282. 10.1159/000117386.PubMedCrossRef
25.
go back to reference Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J: The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007, 175 (9): 926-934. 10.1164/rccm.200607-995OC.PubMedCrossRef Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J: The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007, 175 (9): 926-934. 10.1164/rccm.200607-995OC.PubMedCrossRef
26.
go back to reference Sapey E, Ahmad A, Bayley D, Newbold P, Snell N, Rugman P, Stockley RA: Imbalances between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD. J Clin Immunol. 2009, 29 (4): 508-516. 10.1007/s10875-009-9286-8.PubMedCrossRef Sapey E, Ahmad A, Bayley D, Newbold P, Snell N, Rugman P, Stockley RA: Imbalances between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD. J Clin Immunol. 2009, 29 (4): 508-516. 10.1007/s10875-009-9286-8.PubMedCrossRef
27.
go back to reference Yanbaeva DG, Dentener MA, Creutzberg EC, Wouters EF: Systemic inflammation in COPD: is genetic susceptibility a key factor?. COPD. 2006, 3 (1): 51-61. 10.1080/15412550500493436.PubMedCrossRef Yanbaeva DG, Dentener MA, Creutzberg EC, Wouters EF: Systemic inflammation in COPD: is genetic susceptibility a key factor?. COPD. 2006, 3 (1): 51-61. 10.1080/15412550500493436.PubMedCrossRef
29.
go back to reference Brew K, Dinakarpandian D, Nagase H: Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta. 2000, 1477 (1–2): 267-283. 10.1016/S0167-4838(99)00279-4.PubMedCrossRef Brew K, Dinakarpandian D, Nagase H: Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta. 2000, 1477 (1–2): 267-283. 10.1016/S0167-4838(99)00279-4.PubMedCrossRef
30.
go back to reference Navratilova Z, Zatloukal J, Kriegova E, Kolek V, Petrek M: Simultaneous up- regulation of matrix metalloproteinases 1, 2, 3, 7, 8, 9 and tissue inhibitors of metalloproteinases 1, 4 in serum of patients with chronic obstructive pulmonary disease. Respirology. 2012, 17 (6): 1006-1012. 10.1111/j.1440-1843.2012.02197.x.PubMedCrossRef Navratilova Z, Zatloukal J, Kriegova E, Kolek V, Petrek M: Simultaneous up- regulation of matrix metalloproteinases 1, 2, 3, 7, 8, 9 and tissue inhibitors of metalloproteinases 1, 4 in serum of patients with chronic obstructive pulmonary disease. Respirology. 2012, 17 (6): 1006-1012. 10.1111/j.1440-1843.2012.02197.x.PubMedCrossRef
31.
go back to reference Beeh KM, Beier J, Kornmann O, Buhl R: Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects. Respir Med. 2003, 97 (6): 634-639. 10.1053/rmed.2003.1493.PubMedCrossRef Beeh KM, Beier J, Kornmann O, Buhl R: Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects. Respir Med. 2003, 97 (6): 634-639. 10.1053/rmed.2003.1493.PubMedCrossRef
32.
go back to reference Sethi S, Maloney J, Grove L, Wrona C, Berenson CS: Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006, 173 (9): 991-998. 10.1164/rccm.200509-1525OC.PubMedPubMedCentralCrossRef Sethi S, Maloney J, Grove L, Wrona C, Berenson CS: Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006, 173 (9): 991-998. 10.1164/rccm.200509-1525OC.PubMedPubMedCentralCrossRef
33.
go back to reference D’Armiento JM, Goldklang MP, Hardigan AA, Geraghty P, Roth MD, Connett JE, Wise RA, Sciurba FC, Scharf SM, Thankachen J, Islam M, Ghio AJ, Foronjy RF: Increased matrix metalloproteinase (MMPs) levels do not predict disease severity or progression in emphysema. Plos One. 2013, 8 (2): e56352-10.1371/journal.pone.0056352.PubMedPubMedCentralCrossRef D’Armiento JM, Goldklang MP, Hardigan AA, Geraghty P, Roth MD, Connett JE, Wise RA, Sciurba FC, Scharf SM, Thankachen J, Islam M, Ghio AJ, Foronjy RF: Increased matrix metalloproteinase (MMPs) levels do not predict disease severity or progression in emphysema. Plos One. 2013, 8 (2): e56352-10.1371/journal.pone.0056352.PubMedPubMedCentralCrossRef
Metadata
Title
Compartment differences of inflammatory activity in chronic obstructive pulmonary disease
Authors
Jie Ji
Ida von Schéele
Jan Bergström
Bo Billing
Barbro Dahlén
Ann-Sofie Lantz
Kjell Larsson
Lena Palmberg
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2014
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-014-0104-3

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