The Effect of Experimental Type I Diabetes on Porphyromonas gingivalis-induced Inflammation

Objective: To examine the effects of experimentally induced type 1 diabetes on the inflammatory/immune response induced by Porphyromonas gingivalis and its Lipopolysaccharide (LPS) in mice. Methods: 1. Thioglycollate-elicited peritoneal macrophages were isolated from streptozotocin-induced diabetic and non-diabetic mice and stimulated with 2 concentrations (1 and 10 µg/ml) of P. gingivalis LPS, INF-g (20ng/ml) and a combination of 1 µg/ml LPS and 20 ng/ml INF-g. The levels of TNF-a and nitric oxide (NO) were measured in the culture supernates 20 and 48 hrs after stimulation respectively. Two Titanium chambers were implanted into the subcutaneous tissues of the dorso-lumber region of mice. Two weeks later diabetes was induced in half the animals and a further 2 weeks later all animals received an intrachamber challenge of heat-killed P. gingivalis (10⁹ CFU in 0.1ml PBS). Intra chamber exudates were harvested at baseline and 4 and 24 hrs post-challenge and differential cell counts, TNF-a, INF-g, and IL-10 assessed. Serum antibody titers against P. gingivalis were measured 10 days post challenge. Results: P. gingivalis LPS stimulated macrophages from diabetic mice produced significantly more NO and TNF-a than controls and INF-g significantly enhanced this response. Chamber exudates from diabetics and controls had similar TNF-a and INF-g levels 4 hrs post-challenge. IL-10 increases were significantly higher in diabetic animals than controls. The diabetic animals produced significantly lower titers of IgG antibodies to P. gingivalis than controls. Conclusions: The results suggest that diabetes affects the local secretion of inflammatory mediators at the site of the inflammatory response as well as the humoral immune response in a way that may explain the increased periodontal disease severity seen in diabetes.