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Erschienen in: Clinical Oral Investigations 7/2016

10.11.2015 | Original Article

Can apical periodontitis affect serum levels of CRP, IL-2, and IL-6 as well as induce pathological changes in remote organs?

verfasst von: Jinxiu Zhang, Xiaojing Huang, Bingling Lu, Chengfei Zhang, Zhiyu Cai

Erschienen in: Clinical Oral Investigations | Ausgabe 7/2016

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Abstract

Objectives

The aim of this study was to investigate whether apical periodontitis (AP) could cause systemic cytokine elevation and pathological changes in remote organs in an experimental animal model.

Materials and methods

AP was induced in 36 Sprague Dawley (SD) rats. Serum levels of C-reactive protein (CRP), interleukin 2 (IL-2), and interleukin 6 (IL-6) were measured by enzyme-linked immunosorbent assays at different time intervals (0, 6, 12, 24, 48, and 96 h and 1, 2, 3, 4, 5, and 6 weeks) after pulp exposure. Multiple organs (the aortic arch, myocardium, liver, and spleen) were collected for histological observation. The results were analyzed by one-way analysis of variance (ANOVA).

Results

Serum levels of CRP, IL-2, and IL-6 were significantly elevated at all time points assessed after 6, 24, and 96 h, respectively. The peak values of serum cytokines (CRP 6.363 ± 0.05 ng/ml, IL-2 21.997 ± 0.15 ng/L, and IL-6 2.406 ± 0.02 ng/L) were reached at 1, 4, and 2 weeks, respectively, followed by a decline. Time-dependent reversible histopathological changes were detected in the aortic arch, myocardium, and spleen, whereas irreversible changes were found in the liver.

Conclusions

AP elevated the levels of CRP, IL-2, and IL-6 in rat blood serum, causing reversible changes in the aortic arch, myocardium, and spleen as well as irreversible changes in the liver.

Clinical relevance

AP may trigger a systemic immune response, impair remote organs, and affect the general health of patients.
Literatur
1.
Zurück zum Zitat Billings F (1912) Chronic focal infections and their etiologic relations to arthritis and nephritis. Arch Intern Med 9:484–498CrossRef Billings F (1912) Chronic focal infections and their etiologic relations to arthritis and nephritis. Arch Intern Med 9:484–498CrossRef
2.
Zurück zum Zitat Mattila KJ, Nieminen MS, Valtonen VV, Rasi VP, Kesaniemi YA, Syrjala SL, Jungell PS, Isoluoma M, Hietaniemi K, Jokinen MJ (1989) Association between dental health and acute myocardial infarction. BMJ 298:779–781CrossRefPubMedPubMedCentral Mattila KJ, Nieminen MS, Valtonen VV, Rasi VP, Kesaniemi YA, Syrjala SL, Jungell PS, Isoluoma M, Hietaniemi K, Jokinen MJ (1989) Association between dental health and acute myocardial infarction. BMJ 298:779–781CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Syrjanen J, Peltola J, Valtonen V, Iivanainen M, Kaste M, Huttunen JK (1989) Dental infections in association with cerebral infarction in young and middle-aged men. J Intern Med 225:179–184CrossRefPubMed Syrjanen J, Peltola J, Valtonen V, Iivanainen M, Kaste M, Huttunen JK (1989) Dental infections in association with cerebral infarction in young and middle-aged men. J Intern Med 225:179–184CrossRefPubMed
4.
Zurück zum Zitat Cullinan MP, Seymour GJ (2013) Periodontal disease and systemic illness: will the evidence ever be enough. Periodontol 2000(62):271–286CrossRef Cullinan MP, Seymour GJ (2013) Periodontal disease and systemic illness: will the evidence ever be enough. Periodontol 2000(62):271–286CrossRef
5.
Zurück zum Zitat Gomes MS, Blattner TC, Sant’Ana FM, Grecca FS, Hugo FN, Fouad AF, Reynolds MA (2013) Can apical periodontitis modify systemic levels of inflammatory markers? A systematic review and meta-analysis. J Endod 39:1205–1217CrossRefPubMed Gomes MS, Blattner TC, Sant’Ana FM, Grecca FS, Hugo FN, Fouad AF, Reynolds MA (2013) Can apical periodontitis modify systemic levels of inflammatory markers? A systematic review and meta-analysis. J Endod 39:1205–1217CrossRefPubMed
6.
Zurück zum Zitat Boucher Jr NE, Hanrahan JJ, Kihara FY (1967) Occurrence of C-reactive protein in oral disease. J Dent Res 46:624CrossRefPubMed Boucher Jr NE, Hanrahan JJ, Kihara FY (1967) Occurrence of C-reactive protein in oral disease. J Dent Res 46:624CrossRefPubMed
7.
Zurück zum Zitat Matsushita K, Tajima T, Tomita K, Abeyama K, Maruyama I, Takada H, Nagaoka S (1998) Inflammatory cytokine production and specific antibody responses against possible causative bacteria in patients with multilesional periapical periodontitis. J Endod 24:817–821CrossRefPubMed Matsushita K, Tajima T, Tomita K, Abeyama K, Maruyama I, Takada H, Nagaoka S (1998) Inflammatory cytokine production and specific antibody responses against possible causative bacteria in patients with multilesional periapical periodontitis. J Endod 24:817–821CrossRefPubMed
8.
Zurück zum Zitat Cotti E, Dessi C, Piras A, Flore G, Deidda M, Madeddu C, Zedda A, Longu G, Mercuro G (2011) Association of endodontic infection with detection of an initial lesion to the cardiovascular system. J Endod 37:1624–1629CrossRefPubMed Cotti E, Dessi C, Piras A, Flore G, Deidda M, Madeddu C, Zedda A, Longu G, Mercuro G (2011) Association of endodontic infection with detection of an initial lesion to the cardiovascular system. J Endod 37:1624–1629CrossRefPubMed
9.
Zurück zum Zitat Lins L, Bittencourt PL, Evangelista MA, Lins R, Codes L, Cavalcanti AR, Parana R, Bastos J (2011) Oral health profile of cirrhotic patients awaiting liver transplantation in the Brazilian Northeast. Transplant Proc 43:1319–1321CrossRefPubMed Lins L, Bittencourt PL, Evangelista MA, Lins R, Codes L, Cavalcanti AR, Parana R, Bastos J (2011) Oral health profile of cirrhotic patients awaiting liver transplantation in the Brazilian Northeast. Transplant Proc 43:1319–1321CrossRefPubMed
10.
Zurück zum Zitat Costa TH, de Figueiredo Neto JA, de Oliveira AE, Lopes e Maia Mde F, de Almeida AL (2014) Association between chronic apical periodontitis and coronary artery disease. J Endod 40:164–167 Costa TH, de Figueiredo Neto JA, de Oliveira AE, Lopes e Maia Mde F, de Almeida AL (2014) Association between chronic apical periodontitis and coronary artery disease. J Endod 40:164–167
11.
Zurück zum Zitat Gomes MS, Hugo FN, Hilgert JB, Sant’Ana FM, Padilha DM, Simonsick EM, Ferrucci L, Reynolds MA (2015) Apical periodontitis and incident cardiovascular events in the Baltimore Longitudinal Study of Ageing. Int Endod J. doi:10.1111/iej.12468 Gomes MS, Hugo FN, Hilgert JB, Sant’Ana FM, Padilha DM, Simonsick EM, Ferrucci L, Reynolds MA (2015) Apical periodontitis and incident cardiovascular events in the Baltimore Longitudinal Study of Ageing. Int Endod J. doi:10.​1111/​iej.​12468
12.
Zurück zum Zitat Marton IJ (2007) The influence of chronic apical periodontitis on oral and general health. Fogorv Sz 100(200–209):193–199 Marton IJ (2007) The influence of chronic apical periodontitis on oral and general health. Fogorv Sz 100(200–209):193–199
13.
Zurück zum Zitat Kerekes K, Olsen I (1990) Similarities in the microfloras of root canals and deep periodontal pockets. Endod Dent Traumatol 6:1–5CrossRefPubMed Kerekes K, Olsen I (1990) Similarities in the microfloras of root canals and deep periodontal pockets. Endod Dent Traumatol 6:1–5CrossRefPubMed
14.
Zurück zum Zitat Rupf S, Kannengiesser S, Merte K, Pfister W, Sigusch B, Eschrich K (2000) Comparison of profiles of key periodontal pathogens in periodontium and endodontium. Endod Dent Traumatol 16:269–275CrossRefPubMed Rupf S, Kannengiesser S, Merte K, Pfister W, Sigusch B, Eschrich K (2000) Comparison of profiles of key periodontal pathogens in periodontium and endodontium. Endod Dent Traumatol 16:269–275CrossRefPubMed
15.
Zurück zum Zitat Silva TA, Garlet GP, Fukada SY, Silva JS, Cunha FQ (2007) Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. J Dent Res 86:306–319CrossRefPubMed Silva TA, Garlet GP, Fukada SY, Silva JS, Cunha FQ (2007) Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. J Dent Res 86:306–319CrossRefPubMed
18.
Zurück zum Zitat Cantrell DA, Smith KA (1984) The interleukin-2 T-cell system: a new cell growth model. Science 224:1312–1316CrossRefPubMed Cantrell DA, Smith KA (1984) The interleukin-2 T-cell system: a new cell growth model. Science 224:1312–1316CrossRefPubMed
19.
20.
Zurück zum Zitat Brandt C, Pedersen BK (2010) The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol 2010:520258CrossRefPubMedPubMedCentral Brandt C, Pedersen BK (2010) The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol 2010:520258CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Garrido M, Dezerega A, Bordagaray MJ, Reyes M, Vernal R, Melgar-Rodriguez S, Ciuchi P, Paredes R, Garcia-Sesnich J, Ahumada-Montalva P, Hernandez M (2015) C-reactive protein expression is up-regulated in apical lesions of endodontic origin in association with interleukin-6. J Endod 41:464–469CrossRefPubMed Garrido M, Dezerega A, Bordagaray MJ, Reyes M, Vernal R, Melgar-Rodriguez S, Ciuchi P, Paredes R, Garcia-Sesnich J, Ahumada-Montalva P, Hernandez M (2015) C-reactive protein expression is up-regulated in apical lesions of endodontic origin in association with interleukin-6. J Endod 41:464–469CrossRefPubMed
22.
Zurück zum Zitat Kawashima N, Stashenko P (1999) Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation. Arch Oral Biol 44:55–66CrossRefPubMed Kawashima N, Stashenko P (1999) Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation. Arch Oral Biol 44:55–66CrossRefPubMed
23.
Zurück zum Zitat Stashenko P, Yu SM (1989) T helper and T suppressor cell reversal during the development of induced rat periapical lesions. J Dent Res 68:830–834CrossRefPubMed Stashenko P, Yu SM (1989) T helper and T suppressor cell reversal during the development of induced rat periapical lesions. J Dent Res 68:830–834CrossRefPubMed
24.
Zurück zum Zitat Marton IJ, Kiss C (2014) Overlapping protective and destructive regulatory pathways in apical periodontitis. J Endod 40:155–163CrossRefPubMed Marton IJ, Kiss C (2014) Overlapping protective and destructive regulatory pathways in apical periodontitis. J Endod 40:155–163CrossRefPubMed
25.
Zurück zum Zitat Koenen HJ, Smeets RL, Vink PM, van Rijssen E, Boots AM, Joosten I (2008) Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 112:2340–2352CrossRefPubMed Koenen HJ, Smeets RL, Vink PM, van Rijssen E, Boots AM, Joosten I (2008) Human CD25highFoxp3pos regulatory T cells differentiate into IL-17-producing cells. Blood 112:2340–2352CrossRefPubMed
26.
Zurück zum Zitat Morimoto T, Yamasaki M, Nakata K, Tsuji M, Nakamura H (2008) The expression of macrophage and neutrophil elastases in rat periradicular lesions. J Endod 34:1072–1076CrossRefPubMed Morimoto T, Yamasaki M, Nakata K, Tsuji M, Nakamura H (2008) The expression of macrophage and neutrophil elastases in rat periradicular lesions. J Endod 34:1072–1076CrossRefPubMed
27.
Zurück zum Zitat Tsuji M, Yamasaki M, Amano K, Matsui H, Morimoto T, Nakamura H (2009) Histochemical localization of neutral proteases released during development of rat periradicular lesion. Arch Oral Biol 54:1128–1135CrossRefPubMed Tsuji M, Yamasaki M, Amano K, Matsui H, Morimoto T, Nakamura H (2009) Histochemical localization of neutral proteases released during development of rat periradicular lesion. Arch Oral Biol 54:1128–1135CrossRefPubMed
28.
Zurück zum Zitat Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB (1997) Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 349:462–466CrossRefPubMed Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB (1997) Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 349:462–466CrossRefPubMed
29.
Zurück zum Zitat Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A, Hutchinson WL, Pepys MB (1999) C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 99:237–242CrossRefPubMed Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A, Hutchinson WL, Pepys MB (1999) C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 99:237–242CrossRefPubMed
30.
Zurück zum Zitat Lindmark E, Diderholm E, Wallentin L, Siegbahn A (2001) Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or noninvasive strategy. Jama 286:2107–2113CrossRefPubMed Lindmark E, Diderholm E, Wallentin L, Siegbahn A (2001) Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or noninvasive strategy. Jama 286:2107–2113CrossRefPubMed
31.
Zurück zum Zitat Ridker PM, Rifai N, Stampfer MJ, Hennekens CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767–1772CrossRefPubMed Ridker PM, Rifai N, Stampfer MJ, Hennekens CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767–1772CrossRefPubMed
32.
Zurück zum Zitat Gimeno D, Delclos GL, Ferrie JE, De Vogli R, Elovainio M, Marmot MG, Kivimaki M (2011) Association of CRP and IL-6 with lung function in a middle-aged population initially free from self-reported respiratory problems: the Whitehall II study. Eur J Epidemiol 26:135–144CrossRefPubMedPubMedCentral Gimeno D, Delclos GL, Ferrie JE, De Vogli R, Elovainio M, Marmot MG, Kivimaki M (2011) Association of CRP and IL-6 with lung function in a middle-aged population initially free from self-reported respiratory problems: the Whitehall II study. Eur J Epidemiol 26:135–144CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Garcia-Rio F, Miravitlles M, Soriano JB, Munoz L, Duran-Tauleria E, Sanchez G, Sobradillo V, Ancochea J (2010) Systemic inflammation in chronic obstructive pulmonary disease: a population-based study. Respir Res 11:63CrossRefPubMedPubMedCentral Garcia-Rio F, Miravitlles M, Soriano JB, Munoz L, Duran-Tauleria E, Sanchez G, Sobradillo V, Ancochea J (2010) Systemic inflammation in chronic obstructive pulmonary disease: a population-based study. Respir Res 11:63CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Zuliani G, Ranzini M, Guerra G, Rossi L, Munari MR, Zurlo A, Volpato S, Atti AR, Ble A, Fellin R (2007) Plasma cytokines profile in older subjects with late onset Alzheimer’s disease or vascular dementia. J Psychiatr Res 41:686–693CrossRefPubMed Zuliani G, Ranzini M, Guerra G, Rossi L, Munari MR, Zurlo A, Volpato S, Atti AR, Ble A, Fellin R (2007) Plasma cytokines profile in older subjects with late onset Alzheimer’s disease or vascular dementia. J Psychiatr Res 41:686–693CrossRefPubMed
35.
Zurück zum Zitat Dye BA, Choudhary K, Shea S, Papapanou PN (2005) Serum antibodies to periodontal pathogens and markers of systemic inflammation. J Clin Periodontol 32:1189–1199CrossRefPubMed Dye BA, Choudhary K, Shea S, Papapanou PN (2005) Serum antibodies to periodontal pathogens and markers of systemic inflammation. J Clin Periodontol 32:1189–1199CrossRefPubMed
36.
Zurück zum Zitat Stollberger C, Finsterer J (2002) Role of infectious and immune factors in coronary and cerebrovascular arteriosclerosis. Clin Diagn Lab Immunol 9:207–215PubMedPubMedCentral Stollberger C, Finsterer J (2002) Role of infectious and immune factors in coronary and cerebrovascular arteriosclerosis. Clin Diagn Lab Immunol 9:207–215PubMedPubMedCentral
37.
Zurück zum Zitat Willershausen B, Kasaj A, Willershausen I, Zahorka D, Briseno B, Blettner M, Genth-Zotz S, Munzel T (2009) Association between chronic dental infection and acute myocardial infarction. J Endod 35:626–630CrossRefPubMed Willershausen B, Kasaj A, Willershausen I, Zahorka D, Briseno B, Blettner M, Genth-Zotz S, Munzel T (2009) Association between chronic dental infection and acute myocardial infarction. J Endod 35:626–630CrossRefPubMed
38.
Zurück zum Zitat Aberg F, Helenius-Hietala J, Meurman J, Isoniemi H (2014) Association between dental infections and the clinical course of chronic liver disease. Hepatol Res 44:349–353CrossRefPubMed Aberg F, Helenius-Hietala J, Meurman J, Isoniemi H (2014) Association between dental infections and the clinical course of chronic liver disease. Hepatol Res 44:349–353CrossRefPubMed
Metadaten
Titel
Can apical periodontitis affect serum levels of CRP, IL-2, and IL-6 as well as induce pathological changes in remote organs?
verfasst von
Jinxiu Zhang
Xiaojing Huang
Bingling Lu
Chengfei Zhang
Zhiyu Cai
Publikationsdatum
10.11.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Oral Investigations / Ausgabe 7/2016
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-015-1646-6

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