title: Pathogenesis of induced rat periapical lesions.
abstract: Studies of the mechanisms of pathogenesis of periapical lesions were undertaken using a rat model of surgical pulp exposure. In this model, periapical lesions develop rapidly between days 0 and 15 (active phase) and more slowly thereafter (chronic phase). A Gram-negative anaerobic flora, similar to that seen in human beings, are quickly established. Lesions contain a mixed inflammatory cell infiltrate consisting of T cells, neutrophils, B cells, macrophages, and plasma cells. Helper T cells predominate during the active phase, whereas suppressor T cells are more frequent in the chronic phase. Extracts of periapical lesions contain bone-resorbing activity, the highest levels of which are present when lesions are actively expanding. Most bone-resorbing activity is mediated by the cytokine interleukin-1 alpha, as determined by biochemical criteria and antibody neutralization studies. Prostaglandin2 accounts for 10% to 15% of resorptive activity. Cells that express interleukin-1 alpha were identified in pulp beginning on day 2 after exposure and in periapical tissue beginning on day 7, as determined by in situ hybridization and immunostaining. Macrophages, fibroblasts, neutrophils, and osteoclasts were positive for interleukin-1 alpha mRNA and protein. Cells that express tumor necrosis factor alpha were also detected, whereas cells expressing interleukin-1 beta or tumor necrosis factor beta were absent. Finally, periapical bone destruction was inhibited by 60% by treatment with interleukin-1 receptor antagonist. These studies establish a key role for interleukin-1 alpha in the pathogenesis of periapical lesions in the rat model.
authors.affiliation: Department of Cytokine Biology, Forsyth Dental Center, Kanagawa Dental College, and Harvard School of Dental Medicine, Boston, Mass.
authors.forename: P
authors.initials: P
authors.lastname: Stashenko
authors.forename: C Y
authors.initials: CY
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Tani-Ishii
authors.forename: S M
authors.initials: SM
authors.lastname: Yu
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology* / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003789:Dental Pulp Exposure / Q000150:complications / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D006089:Gram-Negative Anaerobic Bacteria / Q000472:pathogenicity; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000502:physiology; D008214:Lymphocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010485:Periapical Periodontitis / Q000209:etiology* / Q000276:immunology; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha