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

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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.

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References

  1. Billings F (1912) Chronic focal infections and their etiologic relations to arthritis and nephritis. Arch Intern Med 9:484–498

    Article  Google Scholar 

  2. 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 298:779–781

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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 225:179–184

    Article  PubMed  Google Scholar 

  4. Cullinan MP, Seymour GJ (2013) Periodontal disease and systemic illness: will the evidence ever be enough. Periodontol 2000(62):271–286

    Article  Google Scholar 

  5. 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 39:1205–1217

    Article  PubMed  Google Scholar 

  6. Boucher Jr NE, Hanrahan JJ, Kihara FY (1967) Occurrence of C-reactive protein in oral disease. J Dent Res 46:624

    Article  PubMed  Google Scholar 

  7. 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 24:817–821

    Article  PubMed  Google Scholar 

  8. 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 37:1624–1629

    Article  PubMed  Google Scholar 

  9. 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 43:1319–1321

    Article  PubMed  Google Scholar 

  10. 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. 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. Marton IJ (2007) The influence of chronic apical periodontitis on oral and general health. Fogorv Sz 100(200–209):193–199

    Google Scholar 

  13. Kerekes K, Olsen I (1990) Similarities in the microfloras of root canals and deep periodontal pockets. Endod Dent Traumatol 6:1–5

    Article  PubMed  Google Scholar 

  14. 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 16:269–275

    Article  PubMed  Google Scholar 

  15. Silva TA, Garlet GP, Fukada SY, Silva JS, Cunha FQ (2007) Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. J Dent Res 86:306–319

    Article  PubMed  Google Scholar 

  16. Li X, Kolltveit KM, Tronstad L, Olsen I (2000) Systemic diseases caused by oral infection. Clin Microbiol Rev 13:547–558

    Article  PubMed  PubMed Central  Google Scholar 

  17. Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111:1805–1812

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cantrell DA, Smith KA (1984) The interleukin-2 T-cell system: a new cell growth model. Science 224:1312–1316

    Article  PubMed  Google Scholar 

  19. Smith KA (1988) Interleukin-2: inception, impact, and implications. Science 240:1169–1176

    Article  PubMed  Google Scholar 

  20. Brandt C, Pedersen BK (2010) The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol 2010:520258

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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 41:464–469

    Article  PubMed  Google Scholar 

  22. Kawashima N, Stashenko P (1999) Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation. Arch Oral Biol 44:55–66

    Article  PubMed  Google Scholar 

  23. Stashenko P, Yu SM (1989) T helper and T suppressor cell reversal during the development of induced rat periapical lesions. J Dent Res 68:830–834

    Article  PubMed  Google Scholar 

  24. Marton IJ, Kiss C (2014) Overlapping protective and destructive regulatory pathways in apical periodontitis. J Endod 40:155–163

    Article  PubMed  Google Scholar 

  25. 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 112:2340–2352

    Article  PubMed  Google Scholar 

  26. Morimoto T, Yamasaki M, Nakata K, Tsuji M, Nakamura H (2008) The expression of macrophage and neutrophil elastases in rat periradicular lesions. J Endod 34:1072–1076

    Article  PubMed  Google Scholar 

  27. 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 54:1128–1135

    Article  PubMed  Google Scholar 

  28. 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 349:462–466

    Article  PubMed  Google Scholar 

  29. 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 99:237–242

    Article  PubMed  Google Scholar 

  30. 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 286:2107–2113

    Article  PubMed  Google Scholar 

  31. 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 101:1767–1772

    Article  PubMed  Google Scholar 

  32. 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 26:135–144

    Article  PubMed  PubMed Central  Google Scholar 

  33. 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 11:63

    Article  PubMed  PubMed Central  Google Scholar 

  34. 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 41:686–693

    Article  PubMed  Google Scholar 

  35. Dye BA, Choudhary K, Shea S, Papapanou PN (2005) Serum antibodies to periodontal pathogens and markers of systemic inflammation. J Clin Periodontol 32:1189–1199

    Article  PubMed  Google Scholar 

  36. Stollberger C, Finsterer J (2002) Role of infectious and immune factors in coronary and cerebrovascular arteriosclerosis. Clin Diagn Lab Immunol 9:207–215

    PubMed  PubMed Central  Google Scholar 

  37. 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 35:626–630

    Article  PubMed  Google Scholar 

  38. Aberg F, Helenius-Hietala J, Meurman J, Isoniemi H (2014) Association between dental infections and the clinical course of chronic liver disease. Hepatol Res 44:349–353

    Article  PubMed  Google Scholar 

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Acknowledgments

We are very grateful to the Comparative Medicine Department of Fuzhou General Hospital of Nanjing Military Command for their assistance with the animal experiments.

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Authors and Affiliations

  1. Department of Endodontics and Operative Dentistry, School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, Fujian, 350002, China

    Jinxiu Zhang, Xiaojing Huang & Bingling Lu

  2. Comprehensive Dental Care, Endodontics, Faculty of Dentistry, The University of Hong Kong, Prince Philip Dental Hospital, 34 Hospital Road, Hong Kong, SAR, China

    Chengfei Zhang

  3. Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, 350002, China

    Zhiyu Cai

  4. School and Hospital of Stomatology, Fujian Medical University, 246 Yangqiao Zhong Road, Fuzhou, Fujian, 350002, China

    Zhiyu Cai

Authors
  1. Jinxiu Zhang
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  2. Xiaojing Huang
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  3. Bingling Lu
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  4. Chengfei Zhang
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  5. Zhiyu Cai
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Corresponding author

Correspondence to Xiaojing Huang.

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Funding

This study was funded by the National Natural Science Foundation of China (grant no. 81271131) and the Key Project of the Natural Science Foundation of Fujian Province, China (grant no. 2012Y0029).

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Zhang, J., Huang, X., Lu, B. et al. Can apical periodontitis affect serum levels of CRP, IL-2, and IL-6 as well as induce pathological changes in remote organs?. Clin Oral Invest 20, 1617–1624 (2016). https://doi.org/10.1007/s00784-015-1646-6

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  • DOI: https://doi.org/10.1007/s00784-015-1646-6

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