Are comorbidities associated with the cytokine/chemokine profile of persistent apical periodontitis?

Clin Oral Investig. 2023 Sep;27(9):5203-5215. doi: 10.1007/s00784-023-05139-3. Epub 2023 Jul 11.

Abstract

Objectives: This study aimed to identify disease-related markers in persistent apical periodontitis (PAP) biopsies and examine whether these were associated with comorbidities like rheumatoid arthritis (RA) and cardiovascular diseases (CVD).

Materials and method: The levels of the cytokines/chemokines GM-CSF, IFN-γ, IL-2, IL-6, IL-9, IL-10, IL-13, IL-15, IL-17E/IL-25, IL-21, IL-23, IL-27, IL-28A/IFN -λ2, IL-33, MIP-3α/CCL20, and TNF-α were determined in lesions from patients with PAP (n = 20) and compared to healthy bone samples (n = 20).

Results: We identified eleven cytokines to be differently expressed, and among them, IL-2, IL-6, IL-17E, IL-21, and IL-27 appeared to drive the discrepancy between the disease and healthy groups. The levels of T follicular helper (Tfh) cell promoting cytokines (IL-21, IL-6, IL-27) were enhanced while T helper (Th) 1 cell promoting cytokine (IL-2), Th2 cell promoting cytokine (IL-13), and Th17 cell promoting cytokine (IL-17E) were reduced in the PAP group. The data also indicate that Tfh cell differentiation (IL-21), along with Th1 (GM-CSF, IFNγ), Th2 (IL-13), and Th17 (GM-CSF) cell differentiation, might be increased in the subpopulation of patients suffering from RA, whereas no differences were found in patients with CVD.

Conclusions: Levels of cytokines/chemokines in PAP were identified, and cluster analyzes indicated that these markers may be associated with the differentiation of different T cell populations. Patients with PAP and RA comorbidities showed elevated levels of markers reinforcing this association.

Clinical relevance: Molecular analyses of PAP may result in identification of prognostic markers.

Keywords: Arthritis; Cytokines; Immunology; Periodontal Disease; Persistent Apical Periodontitis.

MeSH terms

  • Arthritis, Rheumatoid*
  • Chemokines
  • Cytokines
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Humans
  • Interleukin-13
  • Interleukin-17
  • Interleukin-2
  • Interleukin-27*
  • Interleukin-6

Substances

  • Cytokines
  • Interleukin-17
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Interleukin-13
  • Interleukin-2
  • Interleukin-27
  • Interleukin-6
  • Chemokines