Social stress increases cytokine production by Porphyromonas gingivalis LPS-stimulated macrophages

Objectives: Stress is a risk indicator for periodontal diseases, but a causal mechanism has not yet been defined. To address the hypothesis that the inflammatory response to oral pathogens is exacerbated by stress, experiments were conducted to assess whether macrophages from mice exposed to the social stressor called social disruption (SDR) would produce higher levels of inflammatory cytokines when stimulated with LPS from Porphyromonas gingivalis.

Methods: Male CD-1 outbred mice were exposed to the social stressor (SDR), which involved aggressive interactions between 5 resident mice and an aggressive intruder. These interactions occurred over a 2-hr period repeated for 6 consecutive days. After SDR, mice were sacrificed and flow cytometry was used to phenotype cell populations in the spleen. Macrophages from the spleen were positively selected and stimulated with LPS derived from P. gingivalis (1 µg/ml). After 18 hrs in culture, the supernatants were collected and the levels of IL-1â and TNF-á were quantified via ELISA.

Results: In concurrence with previous studies, SDR resulted in a significant increase in the numbers of monocytes/macrophages in the spleen (p < .05). Exposure to SDR prior to ex vivo LPS stimulation significantly increased the production of both IL-1â and TNF-á by total splenocytes (p < .05) and by splenic macrophages (p < .05).

Conclusions: These data support the hypothesis that macrophage cytokine production induced by LPS from the oral pathogen P. gingivalis is enhanced by SDR and provide the rational to develop animal models to study the mechanisms through which stress affects oral diseases.

Supported by OSU College of Dentistry Seed grant and NIH grant MH046801-15.