Hypothalamic-pituitary-adrenal axis activation by experimental periodontaldisease in rats

Organisms respond to inflammatory conditions by mounting a co-ordinated com plex series of adaptive responses involving the immune, nervous and endocri ne systems that are aimed at restoring the homeostatic balance. We have rec ently shown in a rat model that inappropriate hypothalamic-pituitary-adrena l (HPA) axis regulation and a subsequent inability to mount a suitable gluc ocorticoid response to gingival inflammation may influence susceptibility t o periodontal disease. This study was designed to investigate whether ligat ure- and bacterial lipopolysaccharide (LPS)-induced inflammation in the gin gival connective tissues may activate this physiological axis, and to furth er explore the significance of HPA regulation in periodontal disease. Exper imental periodontal disease was induced in major histocompability complex ( MHC)-identical but HPA low (LEW) and high (F344) responding rat strains. We tested (1) whether ongoing periodontal disease activates the HPA axis as m easured by corticosterone levels, and (2) whether genetic differences in HP A regulation modulate periodontal disease progression. In the F344 strain, the periodontal tissue destruction was more severe. This observation was as sociated with a significant increase of corticosterone levels in F344 rats only. Addition of LPS at the gingival inflammatory site led to a further in crease of corticosterone levels and disease severity in F344 rats. These fi ndings illustrate a positive feedback loop between the HPA axis and periodo ntal disease: the disease activates the HPA axis, and a genetically determi ned high HPA responsitivity further increases disease susceptibility.