RESUMEN
The objective of this study is to detrmine whether alloxan-induced diabetic Lactoferrin knockout (LFKO-/-) mice are more susceptible to periodontal disease caused by Aggregatibacter actinomycetemcomitans compared to the diabetic wild-type (WT) mice. Diabetes was induced in mice by a single dose of alloxan (60 mg/kg) injected intravenously. Mice were categorized as diabetic when blood glucose levels >250 mg/dL were measured on the 7th day after the injection. Periodontal disease was experimentally induced by A. actinomycetemcomitans infection in alloxan induced diabetic WT and LFKO-/- mice. Fasting blood glucose levels and body weight were monitored throughout the study. At the end of the 12th week of infection, mice were sacrificed and bone loss among the groups was estimated by measuring the distance between cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) at 12 sites on the molars. A. actinomycetemcomitans infected mice groups developed more alveolar bone loss than sham-infected animals. Diabetic LFKO-/- infected mice exhibited significant bone loss (P<0.01) and a higher mean fasting blood glucose level (P<0.05) when compared to diabetic WT infected mice. No statistically significant difference in fasting blood glucose level was found between the infected and sham-infected groups. Peripheral blood analysis at the end of the 12th week revealed a significant reduction in the platelet counts in LFKO-/- mice when compared to WT mice. Furthermore, diabetic LFKO-/- presented with lower counts than non-diabetic LFKO-/- mice (P<0.01). In conclusion, diabetic lactoferrin deficient mice are at a higher risk of developing periodontal infection induced by A. actinomycetemcomitans when compared to diabetic WTI mice.
RESUMEN
Aggregatibacter actinomycetemcomitans, a periodontopathogen, has been associated with several systemic diseases. Herein, we report the protective effect of human lactoferrin (hLF) during A. actinomycetemcomitans bacteremia in lactoferrin knockout (LFKO(-/-)) mice. The prophylactic, concurrent, and therapeutic intravenous (i.v.) administrations of hLF significantly cleared the bacteria from blood and organs. Nevertheless, all modes of hLF administration significantly decreased the concentrations of serum proinflammatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-10, and IL-12p70. Additionally, hLF administration significantly decreased hepatic and splenic proinflammatory cytokine expression levels compared to those in the non-hLF-treated group. Furthermore, administration of hLF decreased the serum C-reactive protein level, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) gene expression levels in liver and spleen. hLF treatment has also resulted in a 6-fold decrease in spleen weight with the migration of typical inflammatory cells in infected mice as a result of decreased inflammatory response. These results reveal that hLF protects against A. actinomycetemcomitans bacteremia, as indicated by rapid bacterial clearance and decreased host proinflammatory mediators.