INTERLEUKIN-8 PRODUCTION BY POLYMORPHONUCLEAR NEUTROPHILS IN PATIENTSWITH RAPIDLY PROGRESSIVE PERIODONTITIS - AN AMPLIFYING LOOP OF POLYMORPHONUCLEAR NEUTROPHIL ACTIVATION

Polymorphonuclear neutrophils (PMN) are the most abundant immune cells in inflammatory gingival sites of patients with early onset periodont itis, localized juvenile periodontitis, and rapidly progressive period ontitis (RPP). In the latter, the large number of PMN in connective ti ssue may explain the marked gingival destruction. Because interleukin- 8 (IL-8) is a potent PMN chemoattractant, we evaluated circulating lev els and gingival mRNA expression of IL-8. We found high IL-8 plasma le vels as well as strong IL-8 mRNA expression in both epithelial and con nective 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 e xpression of adhesion molecules at the PMN surface as well as the oxid ative burst in whole blood from 14 patients with RPP, using flow cytom etry to avoid irrelevant stimulations and to analyze single cells. In RPP patients, resting PMN showed reduced L-selectin, Lewis x, and sial yl Lewis x antigen expression as well as increased H2O2 production. Th ese modifications of PMN adhesion molecule expression, together with t heir increased basal oxidative burst and excessive IL-8 production, ma y contribute to the noxious inflammatory reaction, which may in turn b e 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 tha t may be involved in the increased susceptibility of RPP patients to i nfection. After appropriate treatment of RPP, the reduction in inflamm ation was associated with a return to control levels of both plasma IL -8 and PMN functions, suggesting that these features are linked.