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Clinical Oral Investigations

, Volume 22, Issue 3, pp 1395–1401 | Cite as

Endodontic infections increase leukocyte and lymphocyte levels in the blood

  • Renata Oliveira Samuel
  • João Eduardo Gomes-Filho
  • Mariane Maffei Azuma
  • Dóris Hissako Sumida
  • Sandra Helena Penha de Oliveira
  • Fernando Yamamoto Chiba
  • Suely Regina Mogami Bomfim
  • Paulo César Ciarlini
  • Luis Gustavo Narciso
  • Luciano Tavares Angelo Cintra
Original Article
  • 230 Downloads

Abstract

Objectives

The aim of this study was to determine whether the presence of single or multiple apical periodontitis (AP) alters blood cell counts and cytokine production.

Material and methods

Thirty rats were divided into three groups: a control group comprising rats without AP, a group called 1AP comprising rats with AP in one tooth, and a group called 4AP comprising rats with AP in four teeth. Endodontic infection was induced by pulp exposure of the first right maxillary molar in the 1AP group or by exposing the first and second right maxillary and mandibular molars in the 4AP group. A blood count and cytokine levels were obtained 30 days after infection by collecting blood by cardiac puncture. The maxillae were dissected and stained with hematoxylin and eosin to evaluate the inflammatory infiltrate. The data were tabulated and subjected to statistical analysis (P < 0.05).

Results

Histological analysis showed a predominance of mononuclear inflammatory cells. In blood, significant increase of leukocytes, lymphocytes, and tumor necrosis factor alpha (TNF-α) in 4AP compared with the control and 1AP groups (P < 0.05) was observed. In addition, significant decrease of interleukin-4 (IL-4) in 1AP and 4AP groups compared with the control was observed (P < 0.05).

Conclusions

In the rat model, the presence of multiple AP can affect health by increasing lymphocyte and TNF-α levels in the blood.

Clinical relevance

The presence of endodontic infections can interfere with the blood profile, altering systemic health.

Keywords

Apical periodontitis Leukocytes Lymphocytes Blood count 

Notes

Funding

This study was supported by a grant (2013/23358-8) from the São Paulo Research Foundation (FAPESP), São Paulo, SP, Brazil.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This article does not contain any studies with human participants performed by any authors. The animal study was approved by the Institutional Ethics Committee (CEUA 2014-00108) of Universidade Estadual Paulista, São Paulo, Brazil and conducted in accordance with ethical standards.

Informed consent

For this type of study, formal consent is not required.

References

  1. 1.
    Márton IJ, Kiss C (2014) Overlapping protective and destructive regulatory pathways in apical periodontitis. J Endod 40:155–163.  https://doi.org/10.1016/j.joen.2013 CrossRefPubMedGoogle Scholar
  2. 2.
    Garlet GP (2010) Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res 89:1349–1363.  https://doi.org/10.1177/0022034510376402 CrossRefPubMedGoogle Scholar
  3. 3.
    Cintra LT, Samuel RO, Azuma MM, Ribeiro CP, Narciso LG, de Lima VM, Sumida DH, Coclete GA, Dezan-Júnior E, Gomes-Filho JE (2014) Apical periodontitis and periodontal disease increase serum IL-17 levels in normoglycemic and diabetic rats. Clin Oral Investig 18:2123–2128.  https://doi.org/10.1007/s00784-014-1192-7 CrossRefPubMedGoogle Scholar
  4. 4.
    Cintra LT, Samuel RO, Facundo AC, Prieto AK, Sumida DH, Bomfim SR, Souza JC, Dezan-Júnior E, Gomes-Filho JE (2014) Relationships between oral infections and blood glucose concentrations or HbA1c levels in normal and diabetic rats. Int Endod J 47:228–237.  https://doi.org/10.1111/iej.12136 CrossRefPubMedGoogle Scholar
  5. 5.
    Marçal JR, Samuel RO, Fernandes D, de Araujo MS, Napimoga MH, Pereira SA, Clemente-Napimoga JT, Alves PM, Mattar R, Rodrigues V Jr, Rodrigues DB (2010) T-helper cell type 17/regulatory T-cell immunoregulatory balance in human radicular cysts and periapical granulomas. J Endod 36:995–999.  https://doi.org/10.1016/j.joen.2010.03.020 CrossRefPubMedGoogle Scholar
  6. 6.
    Liu Y, Yin H, Zhao M, Lu Q (2014) TLR2 and TLR4 in autoimmune diseases: a comprehensive review. Clin Rev Allergy 47:136–147.  https://doi.org/10.1007/s12016-013-8402-y CrossRefGoogle Scholar
  7. 7.
    Linden GJ, Herzberg MC (2013) Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joint EFP/AAP workshop on periodontitis and systemic diseases. J Periodontol 84:S20–S23.  https://doi.org/10.1902/jop.2013.1340020 CrossRefPubMedGoogle Scholar
  8. 8.
    Khalaf H, Lönn J, Bengtsson T (2014) Cytokines and chemokines are differentially expressed in patients with periodontitis: possible role for TGF-β1 as a marker for disease progression. Cytokine 67:29–35.  https://doi.org/10.1016/j.cyto.2014.02.007 CrossRefPubMedGoogle Scholar
  9. 9.
    Morita I, Inagaki K, Nakamura F, Noguchi T, Matsubara T, Yoshii S, Nakagaki H, Mizuno K, Sheiham A, Sabbah W (2012) Relationship between periodontal status and levels of glycated hemoglobin. J Dent Res 91:161–166.  https://doi.org/10.1177/0022034511431583 CrossRefPubMedGoogle Scholar
  10. 10.
    Shimazaki Y, Saito T, Yonemoto K, Kiyohara Y, Iida M, Yamashita Y (2007) Relationship of metabolic syndrome to periodontal disease in Japanese women: the Hisayama Study. J Dent Res 86:271–275CrossRefPubMedGoogle Scholar
  11. 11.
    Cintra LT, da Silva Facundo AC, Azuma MM, Sumida DH, Astolphi RD, Bomfim SR, Narciso LG, Gomes-Filho JE (2013) Pulpal and periodontal diseases increase triglyceride levels in diabetic rats. Clin Oral Investig 17:1595–1599.  https://doi.org/10.1007/s00784-012-0853-7 CrossRefPubMedGoogle Scholar
  12. 12.
    Hendek MK, Erdemir EO, Kisa U, Ozcan G (2014) Effect of initial periodontal therapy on the oxidative stress markers in gingival crevicular fluid, saliva and serum in smokers and non-smokers with chronic periodontitis. J Periodontol 17:1–17.  https://doi.org/10.1902/jop.2014.140338 Google Scholar
  13. 13.
    Cintra LT, da Silva Facundo AC, Prieto AK, Sumida DH, Narciso LG, Mogami Bomfim SR, Oliveira e Silva C, Dezan-Júnior E, Gomes-Filho JE (2014) Blood profile and histology in oral infections associated with diabetes. J Endod 40:1139–1144.  https://doi.org/10.1016/j.joen.2014.01.034 CrossRefPubMedGoogle Scholar
  14. 14.
    Cintra LT, Samuel RO, Prieto AK, Sumida DH, Dezan-Júnior E, Gomes-Filho JE (2017) Oral health, diabetes, and body weight. Arch Oral Biol 73:94–99.  https://doi.org/10.1016/j.archoralbio.2016.10.002 CrossRefPubMedGoogle Scholar
  15. 15.
    Pereira RF, de Oliveira da Mota MS, de Lima Coutinho Mattera MS, Tsosura TV, Chiba FY, Garbin CA, Ervolino E, Cintra LT, Okamoto MM, Machado UF, Sumida DH (2016) Periapical lesions decrease Akt serine phosphorylation and plasma membrane GLUT4 content in rat skeletal muscle. Clin Oral Investig 20:1625–1630.  https://doi.org/10.1007/s00784-015-1664-4 CrossRefPubMedGoogle Scholar
  16. 16.
    Astolphi RD, Curbete MM, Chiba FY, Cintra LT, Ervolino E, da Mota MS, Antoniali C, Garbin CA, Sumida DH (2015) Periapical lesions decrease insulin signaling in rat skeletal muscle. J Endod 41:1305–1310.  https://doi.org/10.1016/j.joen.2015.04.002 CrossRefPubMedGoogle Scholar
  17. 17.
    Cintra LT, Samuel RO, Azuma MM, de Queiróz AO, Ervolino E, Sumida DH, de Lima VM, Gomes-Filho JE (2016) Multiple apical periodontitis influences serum levels of cytokines and nitric oxide. J Endod. 42:747–751.  https://doi.org/10.1016/j.joen.2016.01.022 CrossRefPubMedGoogle Scholar
  18. 18.
    Musalaiah SV, Anupama M, Nagasree M, Krishna CM, Kumar A, Kumar PM (2014) Evaluation of nonsurgical periodontal therapy in chronic periodontitis patients with anemia by estimating hematological parameters and high-sensitivity C-reactive protein levels. J Pharm Bioallied Sci 6:S64–S69.  https://doi.org/10.4103/0975-7406.137390 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Gaddale R, Mudda JA, Karthikeyan I, Desai SR, Shinde H, Deshpande P (2014) Changes in cellular and molecular components of peripheral blood in patients with generalized aggressive periodontitis. J Investig Clin Dent.  https://doi.org/10.1111/jicd.12127
  20. 20.
    Graves D (2008) Cytokines that promote periodontal tissue destruction. J Periodontol 79:1585–1591CrossRefPubMedGoogle Scholar
  21. 21.
    Stein NC, Kreutzmann C, Zimmermann SP, Niebergall U, Hellmeyer L, Goettsch C, Schoppet M, Hofbauer LC (2008) Interleukin-4 and interleukin-13 stimulate the osteoclast inhibitor osteoprotegerin by human endothelial cells through the STAT6 pathway. J Bone Miner Res 23:750–758.  https://doi.org/10.1359/jbmr.080203 CrossRefPubMedGoogle Scholar
  22. 22.
    Liu L, Peng B (2013) The expression of macrophage migration inhibitory factor is correlated with receptor activator of nuclear factor kappa B ligand in induced rat periapical lesions. J Endod 39:984–989.  https://doi.org/10.1016/j.joen.2013.03.001 CrossRefPubMedGoogle Scholar
  23. 23.
    Bian Z, Guo Y, Ha B, Zen K, Liu Y (2012) Regulation of the inflammatory response: enhancing neutrophil infiltration under chronic inflammatory conditions. J Immunol 188:844–853.  https://doi.org/10.4049/jimmunol.1101736 CrossRefPubMedGoogle Scholar
  24. 24.
    Gomes MS, Blattner TC, Sant'Ana Filho M, 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.  https://doi.org/10.1016/j.joen.2013.06.014 CrossRefPubMedGoogle Scholar
  25. 25.
    Gomes MS, Hugo FM, Hilgert JB, Sant'Ana Filho M, Padilha DMP, Simonsick EM (2015) Apical periodontitis and incident cardiovascular events in the Baltimore Longitudinal Study of Aging. Int Endod J.  https://doi.org/10.1111/iej.12468
  26. 26.
    Yu Y, Yang D, Qiu L, Okamura H, Guo J, Haneji T (2014) Tumor necrosis factor-α induces interleukin-34 expression through nuclear factor-κB activation in MC3T3-E1 osteoblastic cells. Mol Med Rep 10:1371–1376.  https://doi.org/10.3892/mmr.2014.2353 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Astolphi RD, Curbete MM, Colombo NH, Shirakashi DJ, Chiba FY, Prieto AK, Cintra LT, Bomfim SR, Ervolino E, Sumida DH (2013) Periapical lesions decrease insulin signal and cause insulin resistance. J Endod 39:648–652.  https://doi.org/10.1016/j.joen.2012.12.031 CrossRefPubMedGoogle Scholar
  28. 28.
    Cotti E, Dessì 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.  https://doi.org/10.1016/j.joen.2011.09.006 CrossRefPubMedGoogle Scholar
  29. 29.
    Colombo NH, Shirakashi DJ, Chiba FY, Coutinho MS, Ervolino E, Garbin CA, Machado UF, Sumida DH (2012) Periodontal disease decreases insulin sensitivity and insulin signaling. J Periodontol 83:864–870.  https://doi.org/10.1902/jop.2011.110349 CrossRefPubMedGoogle Scholar
  30. 30.
    Swain SL, Weinberg AD, English M, Huston G (1990) IL-4 directs the development of Th2-like helper effectors. J Immunol 145:3796–3806PubMedGoogle Scholar
  31. 31.
    Ribeiro FV, de Mendonça AC, Santos VR, Bastos MF, Figueiredo LC, Duarte PM (2011) Cytokines and bone-related factors in systemically healthy patients with chronic periodontitis and patients with type 2 diabetes and chronic periodontitis. J Periodontol 82:1187–1196.  https://doi.org/10.1902/jop.2011.100643 CrossRefPubMedGoogle Scholar
  32. 32.
    Behfarnia P, Birang R, Pishva SS, Hakemi MG, Khorasani MM (2013) Expression levels of th-2 and th-17 characteristic genes in healthy tissue versus periodontitis. J Dent (Tehran) 10:23–31Google Scholar
  33. 33.
    Gemmell E, Marshall RI, Seymour GJ (1997) Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol 2000 14:112–143CrossRefPubMedGoogle Scholar
  34. 34.
    Ruiz-Canela M, Bes-Rastrollo M, Martínez-González MA (2016) The role of dietary inflammatory index in cardiovascular disease, metabolic syndrome and mortality. Int J Mol Sci 17:8.  https://doi.org/10.3390/ijms17081265 CrossRefGoogle Scholar
  35. 35.
    Agarwal N, Kumar VS, Gujjari SA (2009) Effect of periodontal therapy on hemoglobin and erythrocyte levels in chronic generalized periodontitis patients: an interventional study. J Indian Soc Periodontol 13:6–11.  https://doi.org/10.4103/0972-124X.51887 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Anand PS, Sagar DK, Ashok S, Kamath KP (2013) Association of aggressive periodontitis with reduced erythrocyte counts and reduced hemoglobin levels. J Periodontal Res 49:719–728.  https://doi.org/10.1111/jre.12154 CrossRefPubMedGoogle Scholar
  37. 37.
    Domínguez-Sánchez B, López-López J, Jané-Salas E, Castellanos-Cosano L, Velasco-Ortega E, Segura-Egea JJ (2015) Glycated hemoglobin levels and prevalence of apical periodontitis in type 2 diabetic patients. J Endod 41:601–606.  https://doi.org/10.1016/j.joen.2014.12.024 CrossRefGoogle Scholar
  38. 38.
    Clause BT (1993) The Wistar rat as a right choice: establishing mammalian standards and the ideal of a standardized mammal. J Hist Biol 26:329–349CrossRefPubMedGoogle Scholar
  39. 39.
    Ide R, Hoshuyama T, Wilson D, Takahashi K, Higashi T (2011) Periodontal disease and incident diabetes: a seven-year study. J Dent Res 90:41–46.  https://doi.org/10.1177/0022034510381902 CrossRefPubMedGoogle Scholar
  40. 40.
    D'Aiuto F, Suvan J (2012) Obesity, inflammation, and oral infections: are microRNAs the missing link? J Dent Res 91:5–7.  https://doi.org/10.1177/0022034511427164 CrossRefPubMedGoogle Scholar
  41. 41.
    Jia R, Kurita-Ochiai T, Oguchi S, Yamamoto M (2013) Periodontal pathogen accelerates lipid peroxidation and atherosclerosis. J Dent Res 92:247–252.  https://doi.org/10.1177/0022034513475625 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Renata Oliveira Samuel
    • 1
    • 2
  • João Eduardo Gomes-Filho
    • 1
  • Mariane Maffei Azuma
    • 1
    • 3
  • Dóris Hissako Sumida
    • 4
  • Sandra Helena Penha de Oliveira
    • 4
  • Fernando Yamamoto Chiba
    • 4
  • Suely Regina Mogami Bomfim
    • 5
  • Paulo César Ciarlini
    • 5
  • Luis Gustavo Narciso
    • 5
  • Luciano Tavares Angelo Cintra
    • 1
  1. 1.Department of Endodontics, School of DentistrySão Paulo State University (Unesp)AraçatubaBrazil
  2. 2.Department of Clinical Dentistry, Dental SchoolUNIUBE—Universidade de UberabaUberabaBrazil
  3. 3.Department of EndodonticsIngá University Center, UNINGÁMaringáBrazil
  4. 4.Department of Basic Sciences, School of DentistrySão Paulo State University (Unesp)AraçatubaBrazil
  5. 5.Department of Veterinary Clinical Laboratory, School of Veterinary MedicineSão Paulo State University (Unesp)AraçatubaBrazil

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