Interleukin-6 and granulocyte-macrophage colony-stimulating factor in apical periodontitis: correlation with clinical and histologic findings of the involved teeth.

Apical periodontitis is characterized by the presence of immunocompetent cells producing a wide variety of inflammatory mediators. Releasing cytokines with long-range action, such as interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), apical periodontitis may induce changes in remote organs of the host. This study quantified the levels of IL-6 and GM-CSF in symptomatic and asymptomatic human periradicular lesions. Lesions were also characterized by size and histologic findings. Tissue samples were homogenized and supernatants were assayed using an enzyme-linked immunosorbent assay (ELISA). Correlations between cytokine levels and characteristic features (as single variables) of the lesions were analysed. There was a trend for higher levels of IL-6 and GM-CSF in symptomatic than in asymptomatic lesions, but the difference was not significant. Levels also tended to be higher in large than in small lesions, in polymorphonuclear (PMN) cell-rich than in PMN cell-poor samples, and in epithelialized than in non-epithelialized lesions. Significantly higher levels of IL-6 (778.1 +/- 220.5 pg/microg) and GM-CSF (363.3 +/- 98.4 pg/microg) were found in samples coincidentally possessing symptomatic and epithelialized features than in asymptomatic, small, PMN cell-poor, non-epithelialized lesions (IL-6: 45.2 +/- 13.1 pg/microg and GM-CSF: 135.1 +/- 26.4 pg/microg). These results suggest that symptomatic lesions containing epithelial cells represent an immunologically active stage of apical periodontitis, whereas asymptomatic, small, PMN cell-poor, non-epithelialized lesions represent healing apical lesions.

Protective and destructive immune reactions in apical periodontitis.

Apical periodontitis is initiated primarily by the mixed microflora of infected root canals. Continuous flow of bacteria and their products through the apical foramen induces influx, activation and coordinated interaction of immune-inflammatory cells within the periapical area. Successful mobilization of host defense mechanisms prevents abundant extraradicular bacterial invasion. However, anti-infective effector mechanisms are not restricted to killing the invading microorganisms but also destroy normal tissue components and induce bone absorption, resulting ultimately in the loss of the affected teeth. Moreover, autocrine and paracrine loops of stimulation may lead to the perpetuation of the local inflammatory lesion and may also alter the function of remote tissues and organs. This review attempts to summarize current knowledge about the pathogenic mechanism of apical periodontitis, focusing on the formation of a special granulation tissue that effectively fights bacteria originated from the infected pulp chamber and, by exerting this protective function, also contributes to harmful local and distant events. The dynamic equilibrium between defensive and destructive mechanisms may provide a pathobiological basis for better understanding of clinical signs and symptoms of various forms of apical periodontitis lesions and influence treatment strategy and practice.

Differential in situ distribution of interleukin-8, monocyte chemoattractant protein-1 and Rantes in human chronic periapical granuloma.

In situ distribution of three prototype chemokines interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and Rantes was determined in chronic human periapical granulomas by immunohistochemistry using monoclonal antibodies. IL-8 was found primarily in the cytoplasm of the Malassez epithelial cells. MCP-1 immunoreactivity was confined to the endothelial cells that lined small venules. Each of the three investigated chemokines, including Rantes, exhibited a characteristic binding pattern to the extracellular matrix of the lesion. The observed chemokines may play a role in establishing the cellular composition of chronic apical periodontitis, thus augmenting the intensity of local inflammation and tissue damage.

Distribution of interleukin-2 receptor alpha-chain and cells expressing major histocompatibility complex class II antigen in chronic human periapical lesions.

In situ distribution of CD2+ T-lymphocytes, CD4+ and CD8+ T-cell subsets, CD14+ macrophages, interleukin-2 receptor alpha-chain (IL-2R alpha) and class II major histocompatibility complex antigen (major histocompatibility complex class II, HLA-DR) expressing cells were determined in 14 chronic human periapical granulomas by immunohistochemical method using monoclonal antibodies. CD2+ lymphocytes were rather evenly distributed within the classical granulation tissue and comprised 55% of the mononuclear cells. Macrophages were distributed all over the periapical area, but their proportion was much less than that of T lymphocytes. Both small, lymphocyte-like mononuclear cells and larger mononuclear cells resembling macrophages displayed mild to strong circumferential staining with the anti-HLA-DR antibody. The majority of lymphocytes expressed IL-2R alpha indicating the activated state of T cells within the lesion.

The role of reactive oxygen intermediates in the pathogenesis of chronic apical periodontitis.

The level of malondialdehyde, a stable end product of lipid peroxidation induced by reactive oxygen intermediates and the activity of two potent antioxidant enzymes, superoxide dismutase and glutathione peroxidase, was investigated in tissue homogenates of 22 surgical periapical granuloma specimens. Malondialdehyde levels were significantly higher and glutathione peroxidase activity was significantly lower in periapical granuloma samples than in healthy gingival tissue homogenates, which were used as controls. The activity of superoxide dismutase was similar in periapical granuloma and in control samples. Our results indicate an altered balance between the production and the elimination of toxic oxygen metabolites in chronic apical periodontitis. We hypothesize that reactive oxygen intermediates, which are being produced by activated phagocytic cells abundantly present in periapical granulomas, can contribute to periapical tissue injury and bone loss in this disease.

Characterization of inflammatory cell infiltrate in dental periapical lesions.

Sixty-three dental periapical lesions were investigated in order to study the involvement of inflammatory and immunologic reactions in the pathogenesis and maintenance of chronic apical periodontitis. Of 61 well-preserved specimens, 38 were classified as granulomatous, 3 as exudative periapical granulomas and 20 as periapical scars. The quantitative composition of T-lymphocyte subpopulation and macrophages, the proportion of IgE-producing cells compared with other immunoglobulin producing plasma cells, and the tissue distribution of IgE-producing plasma cells compared with that of mast cells were determined in the granulomatous types of granulomas using immunofluorescent, immunohistochemical and enzymehistochemical methods. The results indicated a decreased ratio of helper/inducer versus cytotoxic/suppressor T-lymphocytes, a remarkably high proportion of macrophages, a low frequency of IgE-producing plasma cells with different localization when compared with that of mast cells. These observations suggest that T-lymphocytes and macrophages may play an important role in the complex events of tissue destruction and repair taking place in the periapical region.

Influence of surgical treatment of periapical lesions on serum and blood levels of inflammatory mediators.

Changes in the serum levels of immunoglobulin IgA, IgG, IgM, positive acute phase proteins and complement activity, as well as the lymphocyte subpopulations and the neutrophil leucocyte-related chemiluminescence in the blood of patients with apical granuloma as related to endodontic and surgical treatment were investigated. Measurements were performed on admission, and 7 days and 3 months after the treatment. Elevated IgM concentration, positive acute-phase protein levels and spontaneous whole-blood chemiluminescence were noted at admission. However, a significant decrease in the serum level of each of the six investigated acute-phase proteins, and in the spontaneous chemiluminescence of blood was observed during the 3-month follow-up period. The significant increase in serum complement activity following therapy suggests that complement fixation might have occurred in these patients. A significant increase in the ratio of early sheep erythrocyte rosette-forming lymphocytes was also observed. The results of this study provide evidence for complete recovery after elimination of local inflammation by proper endodontic treatment and apicectomy in patients with apical granuloma.