Effects of periodontitis on the development of asthma: The role of photodynamic therapy

PLoS One. 2017 Nov 16;12(11):e0187945. doi: 10.1371/journal.pone.0187945. eCollection 2017.

Abstract

To evaluate whether periodontitis modulates lung inflammation in an experimental model of asthma as well as the photodynamic therapy (PDT) is associated with a reduction of lung inflammation. Seventy-two BALB/c male mice (~2 months) were randomly divided into 8 groups (n = 9): Basal, Periodontitis (P), P+PT, P+PT+PDT, Asthma (A), A+P, A+P+PT, and A+P+PT+PDT. Periodontitis was induced by using the ligature technique and asthma was induced by ovalbumin (OVA). PT was performed with curettes and PDT with methylene blue (0.005%), λ = 660nm, with a radiant exposure of 318J/cm2. After 43 days, euthanasia was carried out prior to lung and mandible morphological analyzes. All of the manipulations of the animals were performed by only one operator. The total and differential cell counts and cytokines IL-4, IL-5, IL-10, IFN-γ, TNF-α, IL-1β, and IL-6 were evaluated in the bronchoalveolar lavage (BAL) and in the serum. Mucus and alkaline phosphatase were also quantified. Statistical analyzes were performed by a blinded statistician. One-way analysis of variance (ANOVA) was employed, followed by the Student-Newman-Keuls test. Periodontitis group (P) increased alkaline phosphatase and bone resorption (p<0.05), validating the experimental model of periodontitis. The A group and the P group increased the total amount of cells (p <0.05) in the BAL. However, in the A+P group, there was a decrease in these cells, except for in the A+P+PT+PDT group (p<0.05). The asthma group increased the Th2 cytokines and P group increased the Th1 cytokine profile, and A+P+PT+PDT group increased IL-10 cytokine. Mucus was increased for the A and P groups. In conclusion, periodontitis in the asthmatic mice reduced the inflammatory migrated cells in the BAL (eosinophils, lymphocytes, macrophages). In addition, it reduced the levels of the IL-4 and TNF-α cytokines, which was also accompanied by a decreased mucus production. After PDT treatment the total cell count increased however, this increase was not accompanied by a pro-inflammatory cytokines release. Only in PDT group the anti-inflammatory IL-10 was increased. Further studies are needed to understand this mechanism of action.

MeSH terms

  • Animals
  • Asthma / complications*
  • Asthma / metabolism
  • Cytokines / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Periodontitis / complications*
  • Periodontitis / metabolism
  • Photochemotherapy*

Substances

  • Cytokines

Grants and funding

This work was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo -– FAPESP: Process Number #2015/20535-1 (Dr. Anna Carolina Ratto Tempestini Horliana), Process Number #2012/16498-5 (Dr. Ana Paula Ligeiro-Oliveira), Process Number #2015/00830-9 (Dr. Adriana Lino-dos-Santos-Franco) and a Grant from FAPESP # 2015/23152-6 (Nicole Cristine Rigonato-Oliveira- PhD student). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.