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Interleukin-8 production by polymorphonuclear neutrophils in patients with rapidly progressive periodontitis: an
J Gainet1, S Chollet-Martin, M Brion
1Institut National de la Santé et de la Recherché Médicale U479, Service d'Immunologie, Centre Hospitalier Universitaire Xavier Bichat, Paris, France.
Abstract:
Polymorphonuclear neutrophils (PMN) are the most abundant immune cells in inflammatory gingival sites of patients with early onset periodontitis, localized juvenile periodontitis, and rapidly progressive periodontitis (RPP). In the latter, the large number of PMN in connective tissue may explain the marked gingival destruction. Because interleukin-8 (IL-8) is a potent PMN chemoattractant, we evaluated circulating levels and gingival mRNA expression of IL-8. We found high IL-8 plasma levels as well as strong IL-8 mRNA expression in both epithelial and connective gingival cells from patients with RPP. Moreover, the gingival PMN themselves contained IL-8 mRNA, suggesting an autoamplification of PMN recruitment and activation in the gingiva. We also measured the expression of adhesion molecules at the PMN surface as well as the oxidative burst in whole blood from 14 patients with RPP, using flow cytometry to avoid irrelevant stimulations and to analyze single cells. In RPP patients, resting PMN showed reduced L-selectin, Lewis x, and sialyl Lewis x antigen expression as well as increased H2O2 production. These modifications of PMN adhesion molecule expression, together with their increased basal oxidative burst and excessive IL-8 production, may contribute to the noxious inflammatory reaction, which may in turn be autopotentiated by PMN production of IL-8. In addition, PMN showed a lack of increased response (H2O2 production) to formyl peptides after ex vivo priming with IL-8, possibly owing to IL-8 desensitization that may be involved in the increased susceptibility of RPP patients to infection. After appropriate treatment of RPP, the reduction in inflammation was associated with a return to control levels of both plasma IL-8 and PMN functions, suggesting that these features are linked.
Insights
Rapidly progressive periodontitis (RPP) involves high interleukin-8 (IL-8) levels, driving neutrophil accumulation and gingival destruction. PMN in RPP patients exhibit altered function, potentially contributing to disease severity and infection susceptibility.
Area of Science:
- Immunology
- Periodontology
- Cell Biology
Background:
- Polymorphonuclear neutrophils (PMN) are key immune cells in periodontitis.
- Interleukin-8 (IL-8) is a potent chemoattractant for PMN.
- Rapidly progressive periodontitis (RPP) is characterized by severe gingival destruction.
Purpose of the Study:
- To investigate circulating and gingival IL-8 levels in RPP patients.
- To analyze PMN function, including adhesion molecule expression and oxidative burst, in RPP.
- To explore the role of IL-8 in PMN recruitment and activation in RPP.
Main Methods:
- Measurement of plasma IL-8 levels.
- Quantification of gingival IL-8 mRNA expression in epithelial and connective cells.
- Flow cytometry analysis of PMN surface adhesion molecules (L-selectin, Lewis x, sialyl Lewis x) and oxidative burst (H2O2 production) in RPP patients.
- Assessment of PMN response to formyl peptides after IL-8 priming.
Main Results:
- RPP patients exhibited elevated plasma IL-8 and significant IL-8 mRNA expression in gingival tissues.
- Gingival PMN contained IL-8 mRNA, suggesting local autoamplification.
- Resting PMN in RPP patients showed reduced adhesion molecule expression and increased basal H2O2 production.
- PMN from RPP patients demonstrated impaired H2O2 response to formyl peptides after IL-8 priming, indicating potential desensitization.
- Successful RPP treatment normalized plasma IL-8 and PMN functions.
Conclusions:
- Elevated IL-8 and altered PMN function contribute to the inflammatory destruction in RPP.
- PMN-derived IL-8 may potentiate the inflammatory response in RPP.
- IL-8 desensitization in PMN might increase susceptibility to infections in RPP patients.
- Therapeutic interventions reducing inflammation restore IL-8 levels and PMN function in RPP.