Interleukin-8 production by polymorphonuclear neutrophils in patients with 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 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.
Gainet
J
J
Institut National de la Santé et de la Recherché Médicale U479, Service d'Immunologie, Centre Hospitalier Universitaire Xavier Bichat, Paris, France.
Chollet-Martin
S
S
Brion
M
M
Hakim
J
J
Gougerot-Pocidalo
M A
MA
Elbim
C
C
D000328:Adult; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology*; D016877:Oxidants / Q000378:metabolism; D010518:Periodontitis / Q000097:blood / Q000378:metabolism* / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016207:Cytokines; D016209:Interleukin-8; D016877:Oxidants; D012333:RNA, Messenger; D006861:Hydrogen Peroxide