IMMUNOREACTIVITY FOR INTERLEUKIN-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA AND ULTRASTRUCTURAL FEATURES OF MONOCYTES MACROPHAGES IN PERIAPICAL GRANULOMAS

Interleukin 1 (IL-1) and tumor necrosis factor (TNF) have recently been shown to be involved in bone resorption, and because macrophages constitute a significant part of human periapical granulomas, it is reasonable to suspect that they may secrete IL-1 and TNF. The purpose of our investigation was to detect and characterize IL-1-beta- and TNF-alpha-producing cells in human periapical granulomas. Fresh tissue samples obtained during surgery from 10 patients with previously untreated teeth and histologically established periapical granulomas were studied with light and electron microscopy and with immunohistochemical analysis with monoclonal antibodies against IL-1-beta and TNF-alpha. There were very few IL-1-beta+ and TNF-alpha+ cells present in periapical granulomas, and the positive cells had monocyte/macrophage morphology. The IL-1-beta+ cells were located mainly in areas of active exudation and were surrounded by and/or were in close contact with lymphoid cells, whereas TNF-alpha+ cells were scattered and in contact with or near other inflammatory cells at the periphery of active granulation tissue. This suggests that the IL-1-beta+ cells may act in a paracrine manner to activate lymphoid cells. The ultrastructural findings showed that only some macrophages are adapted to extracellular secretion rather than phagocytosis. These modified macrophages could be the major producers of interleukins in tissues. Occasionally, they have plasmacytic or plasmacytoid features resembling the so-called "plasmacytoid monocytes". Only a minor fraction of the monocytes/macrophages (representing about 40% of the inflammatory cells) is an active cytokine-producing state. This fact could suggest a distinct but limited production of these cytokines during tissue chronic inflammation and could explain the limited bone resorption present in periapical granulomas.