Clinical Oral Investigations

, Volume 23, Issue 2, pp 641–650 | Cite as

The ratios of pro-inflammatory to anti-inflammatory cytokines in the serum of chronic periodontitis patients with and without type 2 diabetes and/or smoking habit

  • Tamires Szeremeske Miranda
  • Sílvia Lacerda Heluy
  • Daniele Ferreira Cruz
  • Hélio Doyle Pereira da Silva
  • Magda Feres
  • Luciene Cristina Figueiredo
  • Poliana Mendes DuarteEmail author
Original Article



This study assessed the impact of chronic periodontitis (CP) and CP associated with type 2 diabetes mellitus (DM) and/or smoking on the serum ratios of pro- to anti-inflammatory cytokines.

Materials and methods

Subjects were assigned into one of the following groups: control (n = 25, non-diabetic non-smokers with no history of periodontitis), CP (n = 26, non-diabetic non-smokers with CP), DMCP (n = 30, non-smokers with DM and CP), SCP (n = 27, non-diabetic smokers with CP), and SDMCP (n = 22, smokers with type 2 DM and CP). Serum levels of 18 cytokines were measured using multiplex immunoassays.


Six ratios of pro-inflammatory to anti-inflammatory cytokines were significantly higher in the CP group than in the control group (p < 0.05). Eleven, seventeen and nine ratios of pro-inflammatory to anti-inflammatory cytokines were significantly higher in the DMCP, SCP and SDMCP groups than in the control group, respectively (p < 0.05). The SCP group presented higher serum ratios of tumor necrosis factor (TNF)-α/interleukin (IL)-4, TNF-α/IL-5, IL-17/IL-13 and IL-6/IL-13 (p < 0.05) than the CP group. Cluster analysis revealed a relevant cluster composed of ten cytokines (IL-17, IL-23, interferon-γ, IL-12, IL-1β, IL-2, IL-21, IL-6, IL-4 and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in the serum of subjects from the DMCP group.


The ratios of pro- to anti-inflammatory cytokines shift to favor a pro-inflammatory status in the serum of patients with CP and even more when CP is associated with one or both risk factors.

Clinical relevance

CP and CP associated with hyperglycemia and/or smoking might contribute to a systemic inflammatory burden and increased risk of systemic complications.


Chronic periodontitis Diabetes mellitus Smoking Cytokines 



The work was supported by the São Paulo State Research Foundation (São Paulo, São Paulo, Brazil, no. 2013/10354-4).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study protocol was approved by the Ethics Committee in Clinical Research of the Guarulhos University (CAAE no. 25526913.8.0000.5506).

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Tamires Szeremeske Miranda
    • 1
  • Sílvia Lacerda Heluy
    • 1
  • Daniele Ferreira Cruz
    • 1
  • Hélio Doyle Pereira da Silva
    • 1
  • Magda Feres
    • 1
  • Luciene Cristina Figueiredo
    • 1
  • Poliana Mendes Duarte
    • 1
    Email author
  1. 1.Department of Periodontology, Dental Research DivisionGuarulhos UniversityGuarulhosBrazil

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