Effect of experimental periodontitis on proinflammatory cytokines in the rat

Objective: Our objective was to compare the effects of ligature-induced periodontitis on cytokine concentrations within male and female rats. Methods: Experimental periodontal disease was initiated in age-matched male and female Sprague-Dawley rats by placing a ligature around the second right maxillary molar. Sham-operated male and female control groups were also created. The rats were divided into four groups: females with ligatures (n=9), control females (n=8), males with ligatures (n=10), and control males (n=10). Two weeks later, the right and left maxillary quadrants of molar teeth, liver, omentum, and serum were collected from all the rats. In addition, uterine horns and arteries, and ovaries were collected from the female rats. The tissue samples were ground in PBS (10mg/mL) containing a protease inhibitor and cytokine concentrations were determined by ELISA. Data were compared by factorial ANOVA and post-hoc Tukey test. Results: Female rats with ligatures had higher TNF-α and VEGF concentrations within the uterine horn, IL-6 and CRP within the serum, and CRP within the liver, as compared to controls (p<0.05). In contrast, male animals with ligatures had lower concentrations of CRP and higher IL-6 and TNF-α concentrations within serum, as compared to controls (p<0.05). Concentrations of these biomarkers were significantly higher within both groups of female rats than within both groups of male rats. Conclusions: Experimental periodontitis resulted in both higher serum concentrations of acute phase proteins and uterine proinflammatory cytokines in the female animals. In contrast, experimental periodontitis in the male rats produced significantly different serum concentrations of these biomarkers compared to the female rats. Thus, female rats had a more severe systemic reaction to periodontal inflammation than males, suggesting a mechanism for gender disparities in the incidence of systemic diseases.