Periradicular disease (PRD) : development of a novel explant culture model to investigate the cytokine network
Periradicular disease (PRD), a localised chronic pathologic inflammatory reaction in response to continuous microbial stimuli from necrotic, infected dental root canals, represents a substantial health care burden. The efficacy of available therapies is sub-optimal and identification of new therapeutic targets is essential. Elucidation of functional interactions between PRD cell populations and tissue matrix and between PRD lesion and cells within the surrounding dentoalveolar bone matrix is prerequisite to this. I hypothesise that the cytokine milieu is central in orchestrating these interactions. I generated a novel human explant tissue culture system to investigate the pathogenesis of PRD. I aimed: (1) to investigate the expression of multiple cytokines, but particularly IL-18, within the human lesion and to elucidate their likely biological contribution towards PRD; (2) to investigate the presence of and functional interactions between inflammatory mediators within human PRD that influence bone homeostasis; and (3) to phenotype the contribution of the PRD fibroblast. Four hundred and fifty patients were recruited after obtaining informed consent. PRD tissue was obtained for investigations, of which 310 specimens were examined in a novel explant culture system. Endogenous cytokine release was readily detected in vitro confirming significant inflammatory activity within chronic PRD and facilitating a detailed analysis for the first time of the complex interactions between cytokine activities in PRD.