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 in an active
cytokine-producing state.(ABSTRACT TRUNCATED AT 250 WORDS)