Central European Journal of Medicine

, Volume 9, Issue 5, pp 694–703 | Cite as

Local and systemic immune responses in gingivitis and periodontitis

  • Gediminas ZekonisEmail author
  • Ingrida Barzdziukaite
  • Jonas Zekonis
  • Renata Sadzeviciene
  • Sandrita Simonyte
  • Juozas Zilinskas
Research Article



The aim of this study was to determine the effect of gingivitis and periodontitis on white blood cell (WBC) count and differential WBC count in gingival microvascular blood (GMB) and in venous blood (VB).

Material and methods

102 systemically healthy adult patients — 32 with gingivitis, 36 with periodontitis, and 34 controls — underwent evaluation of the total WBC count, and the count of different types of WBC in VB and GMB.


Inflammation of periodontal tissues was persistently associated with a systemic (in VB) elevation of the WBC count (p<0.05 in gingivitis and p<0.01 in periodontitis), compared to that in control group subjects, and with elevated systemic and local lymphocyte counts (p<0.05), compared to the analogous cell count in the control group. Patients with periodontitis were found to have reduced polymorphonuclear leucocyte (PMN) counts in GMB, compared to patients with gingivitis.


Persistent chronic bacterial infection affects the systemic elevation of WBC in subjects with gingivitis and periodontitis. A local decrease in PMN in periodontitis patients and a systemic increase in lymphocytes in gingivitis and periodontitis patients may indicate the inability of these patients’ organisms to defend against periodontopathic bacteria — and thus susceptibility to disease.


Gingival microvascular blood White blood cell count Periodontitis Gingivitis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Pussinen PJ, Paju S, Mäntylä P, Sorsa T. Serum microbial- and host-derived markers of periodontal diseases: a review. Curr Med Chem 2007;14:2402–2412PubMedCrossRefGoogle Scholar
  2. [2]
    Kinane DF, Lappin DF. Clinical, pathological and immunological aspects of periodontal disease. Acta Odontol Scand 2001;59:154–160PubMedCrossRefGoogle Scholar
  3. [3]
    Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS. Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontol 2000 1997;14:216–248CrossRefGoogle Scholar
  4. [4]
    Ebersole JL, Taubman MA. The protective nature of host responses in periodontal diseases. Periodontol 2000 1994;5:112–141CrossRefGoogle Scholar
  5. [5]
    Di Benedetto A, Gigante I, Colucci S, Grano M. Periodontal disease: linking the primary inflammation to bone loss. Clin Dev Immunol. 2013;2013:503754PubMedCentralPubMedCrossRefGoogle Scholar
  6. [6]
    Mahanonda R, Pichyangkul S. Toll-like receptors and their role in periodontal health and disease. Periodontol 2000. 2007;43:41–55PubMedCrossRefGoogle Scholar
  7. [7]
    Hirschfeld M, Ma Y, Weis JH, Vogel SN, Weis JJ. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol. 2000;165(2):618–622PubMedCrossRefGoogle Scholar
  8. [8]
    Wang PL, Azuma Y, Shinohara M, Ohura K. Tolllike receptor 4-mediated signal pathway induced by Porphyromonas gingivalis lipopolysaccharide in human gingival fibroblasts. Biochem Biophys Res Commun. 2000 Jul 14;273(3):1161–1167PubMedCrossRefGoogle Scholar
  9. [9]
    Hans M, Hans VM. Toll-like receptors and their dual role in periodontitis: a review. J Oral Sci. 2011 Sep;53(3):263–7261PubMedCrossRefGoogle Scholar
  10. [10]
    Hayashi C, Gudino CV, Gibson FC 3rd, Genco CA. Review: Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways. Mol Oral Microbiol. 2010;25(5):305–316PubMedCentralPubMedCrossRefGoogle Scholar
  11. [11]
    Morandini AC, Sipert CR, Gasparoto TH, Greghi SL, Passanezi E, Rezende ML, Sant’ana AP, Campanelli AP, Garlet GP, Santos CF. Differential production of macrophage inflammatory protein-1alpha, stromal-derived factor-1, and IL-6 by human cultured periodontal ligament and gingival fibroblasts challenged with lipopolysaccharide from P. gingivalis. J Periodontol. 2010;81(2):310–317PubMedCrossRefGoogle Scholar
  12. [12]
    Scheres N, Laine ML, de Vries TJ, Everts V, van Winkelhoff AJ. Gingival and periodontal ligament fibroblasts differ in their inflammatory response to viable Porphyromonas gingivalis. J Periodontal Res. 2010;45(2):262–270PubMedCrossRefGoogle Scholar
  13. [13]
    Jung IH, Lee DE, Yun JH, Cho AR, Kim CS, You YJ, Kim SJ, Choi SH. Anti-inflammatory effect of (−)-epigallocatechin-3-gallate on Porphyromonas gingivalis lipopolysaccharide-stimulated fibroblasts and stem cells derived from human periodontal ligament. J Periodontal Implant Sci. 2012;42(6):185–195PubMedCentralPubMedCrossRefGoogle Scholar
  14. [14]
    Kirkwood KL, Cirelli JA, Rogers JE, Giannobile WV. Novel host response therapeutic approaches to treat periodontal diseases. Periodontol 2000. 2007;43:294–315PubMedCentralPubMedCrossRefGoogle Scholar
  15. [15]
    Inoue K, Kobayashi Y, Hanamura H, Toyokawa S. Association of periodontitis with increased white blood cell count and blood pressure. Blood Press 2005;14:53–58PubMedCrossRefGoogle Scholar
  16. [16]
    Hussain Bokhari SA, Khan AA, Tatakis DN, Azhar M, Hanif M, Izhar M. Non-surgical periodontal therapy lowers serum inflammatory markers: a pilot study. J Periodontol 2009;80:1574–1580PubMedCrossRefGoogle Scholar
  17. [17]
    Renvert S, Ohlsson O, Pettersson T, Persson GR. Periodontitis: a future risk of acute coronary syndrome? A follow-up study over 3 years. J Periodontol 2010;81:992–1000PubMedCrossRefGoogle Scholar
  18. [18]
    Christan C, Dietrich T, Hägewald S, Kage A, Bernimoulin JP. White blood cell count in generalized aggressive periodontitis after non-surgical therapy. J Clin Periodontol 2002;29:201–206PubMedCrossRefGoogle Scholar
  19. [19]
    Radafshar G, Shad B, Ariamaid E, Geranmayeh S. Effect of intensive non-surgical treatment of the level of serum inflammatory markers in advanced periodontitis. J. Dent (Tehran) 2010;7(1):24–30Google Scholar
  20. [20]
    Attström R. Presence of leukocytes in crevices of healthy and chronically inflamed gingivae. J Periodontal Res 1970;5:42–47PubMedCrossRefGoogle Scholar
  21. [21]
    Tsukamoto Y, Usui M, Yamamoto G, Takagi Y, Tachikawa T, Yamamoto M, Nakamura M. Role of the junctional epithelium in periodontal innate defense and homeostasis. J Periodontal Res. 2012;47(6):750–757PubMedCrossRefGoogle Scholar
  22. [22]
    Van Dyke TE, Hopp GA. Neutrophil function and oral disease. Crit Rev Oral Biol Med 1990;1: 117–133PubMedGoogle Scholar
  23. [23]
    Laine ML, Crielaard W, Loos BG. Genetic susceptibility to periodontitis. Periodontol 2000. 2012;58(1):37–68Google Scholar
  24. [24]
    Chai L, Song YQ, Leung WK. Genetic polymorphism studies in periodontitis and Fcγ receptors. J Periodontal Res. 2012;47(3):273–285PubMedCrossRefGoogle Scholar
  25. [25]
    Mousavi Jazi M, Solgi G, Asl Roosta H, Noshad S, Moslemi N, Sadrimanesh R, Moradi B, A Amirzargar A. HLA-DRB and HLA-DQA/HLA-DQB allele and haplotype frequencies in Iranian patients with aggressive periodontitis. J Periodontal Res. 2013;48(4):533–539PubMedCrossRefGoogle Scholar
  26. [26]
    Loos BG, John RP, Laine ML. Identification of genetic risk factors for periodontitis and possible mechanisms of action. J Clin Periodontol. 2005;32Suppl 6:159–179PubMedCrossRefGoogle Scholar
  27. [27]
    Tonetti MS, Claffey N; European Workshop in Periodontology group C. Advances in the progression of periodontitis and proposal of definitions of a periodontitis case and disease progression for use in risk factor research. Group C consensus report of the 5th European Workshop in Periodontology. J Clin Periodontol. 2005;32Suppl 6:210–213PubMedCrossRefGoogle Scholar
  28. [28]
    Baker PJ, Dixon M, Roopenian DC. Genetic control of susceptibility to Porphyromonas gingivalisinduced alveolar bone loss in mice. Infect Immun 2000;68:5864–5868PubMedCentralPubMedCrossRefGoogle Scholar
  29. [29]
    Lama J, Planelles V. Host factors influencing susceptibility to HIV infection and AIDS progression. Retrovirology 2007;25;4:52CrossRefGoogle Scholar
  30. [30]
    Pretzl B, El Sayed N, Cosgarea R, Kaltschmitt J, Kim TS, Eickholz P, Nickles K, Bäumer A. IL-1-polymorphism and severity of periodontal disease. Acta Odontol Scand 2012;70(1):1–6PubMedCrossRefGoogle Scholar
  31. [31]
    Reuss E, Fimmers R, Kruger A, Becker C, Rittner C, Höhler T. Differential regulation of interleukin-10 production by genetic and environmental factors — a twin study. Genes Immun 2002;3:407–413PubMedCrossRefGoogle Scholar
  32. [32]
    Lange DE, Plagmann HC, Eenboom A, Promesberger A. Clinical methods for the objective evaluation of oral hygiene. Dtsch Zahnarztl Z 1977;32:44–47PubMedGoogle Scholar
  33. [33]
    Loe H, Silness J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand 1963;21:533–551PubMedCrossRefGoogle Scholar
  34. [34]
    Hayashi C, Gudino CV, Gibson FC 3rd, Genco CA. Review. Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways. Mol Oral Microbiol 2010;25:305–316Google Scholar
  35. [35]
    Gursoy UK, Marakoglu I, Oztop AY. Relationship between neutrophil functions and severity of periodontitis in obese and/or type 2 diabetic chronic periodontitis patients. Quintessence Int 2008;39:485–489PubMedGoogle Scholar
  36. [36]
    Yagi M, Kantarci A, Iwata T, Omori K, Ayilavarapu S, Ito K, Hasturk H, Van Dyke TE. PDK1 regulates chemotaxis in human neutrophils. J Dent Res 2009;88:1119–1124PubMedCentralPubMedCrossRefGoogle Scholar
  37. [37]
    Sheets SM, Potempa J, Travis J, Casiano CA, Fletcher HM. Gingipains from Porphyromonas gingivalis W83 induce cell adhesion molecule cleavage and apoptosis in endothelial cells. Infect Immun. 2005;73(3):1543–1552PubMedCentralPubMedCrossRefGoogle Scholar
  38. [38]
    Pinchback JS, Taylor BA, Gibbins JR, Hunter N. Microvascular angiopathy in advanced periodontal disease. J Pathol 1996;179:204–209PubMedCrossRefGoogle Scholar
  39. [39]
    Sun Y, Li H, Yang MF, Shu W, Sun MJ, Xu Y. Effects of aging on endotoxin tolerance induced by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli. PLoS One. 2012;7(6):e39224PubMedCentralPubMedCrossRefGoogle Scholar
  40. [40]
    Duncan L, Yoshioka M, Chandad F, Grenier D. Loss of lipopolysaccharide receptor CD14 from the surface of human macrophage-like cells mediated by Porphyromonas gingivalis outer membrane vesicles. Microb Pathog. 2004;36(6):319–325PubMedCrossRefGoogle Scholar
  41. [41]
    Sugawara S, Nemoto E, Tada H, Miyake K, Imamura T, Takada H. Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness. J Immunol. 2000;165(1):411–418PubMedCrossRefGoogle Scholar
  42. [42]
    Inomata M, Ishihara Y, Matsuyama T, Imamura T, Maruyama I, Noguchi T, Matsushita K. Degradation of vascular endothelial thrombomodulin by arginine- and lysine-specific cysteine proteases from Porphyromonas gingivalis. J Periodontol. 2009;80(9):1511–1517PubMedCrossRefGoogle Scholar
  43. [43]
    Loos BG. Systemic effects of periodontitis. Ann R Australas Coll Dent Surg 2006;18:27–29PubMedGoogle Scholar
  44. [44]
    Shaddox LM, Wiedey J, Calderon NL, Magnusson I, Bimstein E, Bidwell JA, Zapert EF, Aukhil I, Wallet SM. Local inflammatory markers and systemic endotoxin in aggressive periodontitis. J Dent Res 2011;90(9):1140–1144PubMedCentralPubMedCrossRefGoogle Scholar
  45. [45]
    Kelly JL, O’Sullivan C, O’Riordain M, O’Riordain D, Lyons A, Doherty J, Mannick JA, Rodrick ML. Is circulating endotoxin the trigger for the systemic inflammatory response syndrome seen after injury? Ann Surg 1997;225(5):530–541PubMedCentralPubMedCrossRefGoogle Scholar
  46. [46]
    Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783–801PubMedCrossRefGoogle Scholar
  47. [47]
    Mydel P, Takahashi Y, Yumoto H, Sztukowska M, Kubica M, Gibson FC 3rd, Kurtz DM Jr, Travis J, Collins LV, Nguyen KA, Genco CA, Potempa J. Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection. PLoS Pathog 2006;2:76CrossRefGoogle Scholar
  48. [48]
    Hajishengallis G, Wang M, Bagby GJ, Nelson S. Importance of TLR2 in early innate immune response to acute pulmonary infection with Porphyromonas gingivalis in mice. J Immunol 2008;181:4141–4149PubMedCentralPubMedCrossRefGoogle Scholar
  49. [49]
    Fredriksson MI, Figueredo CM, Gustafsson A, Bergström KG, Asman BE. Effect of periodontitis and smoking on blood leukocytes and acute-phase proteins. J Periodontol 1999;70:1355–1360PubMedCrossRefGoogle Scholar
  50. [50]
    Wakai K, Kawamura T, Umemura O, Hara Y, Machida J, Anno T, Ichihara Y, Mizuno Y, Tamakoshi A, Lin Y, Nakayama T, Ohno Y. Associations of medical status and physical fitness with periodontal disease. J Clin Periodontol 1999;26:664–672PubMedCrossRefGoogle Scholar
  51. [51]
    Bokhari SA, Khan AA, Butt AK, Azhar M, Hanif M, Izhar M, Tatakis DN. Non-surgical periodontal therapy reduces coronary heart disease risk markers: a randomized controlled trial. J Clin Periodontol. 2012;39(11):1065–1074PubMedCrossRefGoogle Scholar
  52. [52]
    Al-Gwaiz LA, Babay HH. The diagnostic value of absolute neutrophil count, band count and morphologic changes of neutrophils in predicting bacterial infections. Med Princ Pract 2007;16:344–347PubMedCrossRefGoogle Scholar
  53. [53]
    Venuprasad K, Chattopadhyay S, Saha B. CD28 signaling in neutrophil induces T-cell chemotactic factor(s) modulating T-cell response. Hum Immunol 2003;64:38–43PubMedCrossRefGoogle Scholar
  54. [54]
    van Zandbergen G, Klinger M, Mueller A, Dannenberg S, Gebert A, Solbach W, Laskay T. Cutting edge: neutrophil granulocyte serves as a vector for Leishmania entry into macrophages. J Immunol 2004;173:6521–6525PubMedCrossRefGoogle Scholar
  55. [55]
    Yun PL, Decarlo AA, Hunter N. Gingipains of Porphyromonas gingivalis modulate leukocyte adhesion molecule expression induced in human endothelial cells by ligation of CD99. Infect Immun. 2006;74(3):1661–1672PubMedCentralPubMedCrossRefGoogle Scholar
  56. [56]
    Nussbaum G, Shapira L. How has neutrophil research improved our understanding of periodontal pathogenesis? J Clin Periodontol 2011;38 Suppl 11:49–59CrossRefGoogle Scholar
  57. [57]
    Lappin DF, McGregor AM, Kinane DF. The systemic immune response is more prominent than the mucosal immune response in the pathogenesis of periodontal disease. J Clin Periodontol 2003 Sep;30(9):778–786PubMedCrossRefGoogle Scholar
  58. [58]
    Brunetti G, Colucci S, Pignataro P, Coricciati M, Mori G, Cirulli N, Zallone A, Grassi FR, Grano M. T cells support osteoclastogenesis in an in vitro model derived from human periodontitis patients. J Periodontol. 2005;76(10):1675–1680PubMedCrossRefGoogle Scholar
  59. [59]
    Colucci S, Mori G, Brunetti G, Coricciati M, Pignataro P, Oranger A, Cirulli N, Mastrangelo F, Grassi FR, Grano M. Interleukin-7 production by B lymphocytes affects the T cell-dependent osteoclast formation in an in vitro model derived from human periodontitis patients. Int J Immunopathol Pharmacol. 2005;18(3 Suppl):13–19PubMedGoogle Scholar
  60. [60]
    Buhlin K, Hultin M, Norderyd O, Persson L, Pockley AG, Rabe P, Klinge B, Gustafsson A. Risk factors for atherosclerosis in cases with severe periodontitis. J Clin Periodontol 2009;36(7):541–549PubMedCrossRefGoogle Scholar
  61. [61]
    Monteiro AM, Jardini MA, Alves S, Giampaoli V, Aubin EC, Figueiredo Neto AM, Gidlund M. Cardiovascular disease parameters in periodontitis. J Periodontol 2009;80(3):378–388PubMedCrossRefGoogle Scholar
  62. [62]
    Lins RD, Figueiredo CR, Queiroz LM, da Silveira EJ, Freitas Rde A. Immunohistochemical evaluation of the inflammatory response in periodontal disease. Braz Dent J 2008;19(1):9–14PubMedCrossRefGoogle Scholar
  63. [63]
    Jenkins SJ, Ruckerl D, Thomas GD, Hewitson JP, Duncan S, Brombacher F, Maizels RM, Hume DA, Allen JE. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1. J Exp Med. 2013;210(11):2477–2491PubMedCentralPubMedCrossRefGoogle Scholar
  64. [64]
    Tonetti MS. Molecular factors associated with compartmentalization of gingival immune responses and transepithelial neutrophil migration. J Periodontal Res. 1997;32(1 Pt 2):104–109PubMedCrossRefGoogle Scholar
  65. [65]
    Soehnlein O, Zernecke A, Weber C. Neutrophils launch monocyte extravasation by release of granule proteins. Thromb Haemost. 2009;102(2):198–205PubMedGoogle Scholar
  66. [66]
    Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L. Neutrophil secretion products pave the way for inflammatory monocytes. Blood. 2008;112(4):1461–1471PubMedCentralPubMedCrossRefGoogle Scholar
  67. [67]
    Zhou J, Zhang J, Chao J. Porphyromonas gingivalis promotes monocyte migration by activating MMP-9. J Periodontal Res. 2012;47(2):236–242PubMedCrossRefGoogle Scholar
  68. [68]
    Suzuki T, Sugita N, Yoshie H, Hara K. Presence of activated eosinophils, high IgE and sCD23 titers in gingival crevicular fluid of patients with adult periodontitis. J Periodontal Res 1995;30(3):159–166PubMedCrossRefGoogle Scholar
  69. [69]
    Xue FM, Zhang HP, Hao HJ, Shi ZY, Zhou C, Feng B, Yang PC. CD98 Positive Eosinophils Contribute to T Helper 1 Pattern Inflammation. PLoS One. 2012;7(12):e51830PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Gediminas Zekonis
    • 1
    Email author
  • Ingrida Barzdziukaite
    • 1
  • Jonas Zekonis
    • 1
  • Renata Sadzeviciene
    • 1
  • Sandrita Simonyte
    • 1
  • Juozas Zilinskas
    • 2
  1. 1.Lithuanian University of Health SciencesKaunasLithuania
  2. 2.Public institution “Odontologijos studija”KaunasLithuania

Personalised recommendations