Polymorphonuclear neutrophils and their mediators in gingival tissues fromgeneralized aggressive periodontitis

Background: Impaired polymorphonuclear neutrophil (PMN) functions were gene rally considered to be related to the onset of generalized aggressive perio dontitis (GAgP). However, some research has indicated that the hyperreactiv ity of PMN seems to be involved in the inflammatory response of GAgP. The p resent study's main purpose was to provide more evidence about the role of PMN in the pathogenesis of GAgP by surveying PMN infiltration in gingiva an d its relationship with the expression of their mediators including interce llular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), interleukin-1 be ta (IL- 1 beta), and tumor necrosis factor-alpha (TNF-alpha). The inflammat ory response in GAgP was also compared with that in adult periodontitis (AP ) and periodontally healthy subjects. Since these PMN mediators were report ed to be produced mainly by macrophages, the association between the expres sion of these PMN mediators and the distribution of macrophages was also in vestigated. Methods: A total of 25 gingival specimens were obtained from 10 GAgP patien ts, 10 AP patients, and 5 periodontally healthy subjects. Serial sections w ere obtained from each specimen, and the following techniques were adopted to investigate the distribution and interrelation of different cells and cy tokines. Infiltration of PMN was observed by using hematoxylin and eosin st aining. Distribution of the macrophages, identified as CD68(+), was shown b y using immunohistochemistry. Immunohistochemistry and in situ hybridizatio n were used to detect the expression of ICAM-1, IL-8, IL-1 beta, and TNF-al pha in gingival tissues. These techniques were performed in serial sections from each individual specimen. Results: Large numbers of infiltrating PMNs were observed in gingiva from G AgP. In gingiva from both GAgP and AP, the strongest protein and mRNA expre ssion of IL-8, ICAM-1, IL-1 beta, and TNF-alpha were located in pocket epit helium and adjacent connective tissue with large numbers of infiltrating PM Ns. In tissues without abundant PMN infiltration, the appearance of positiv e cells expressing IL-8, ICAM-1, IL-1 beta, and TNF-alpha was scattered. CD 68(+) was distributed sparsely in connective tissue and was hardly seen in pocket epithelium with large numbers of PMN infiltration. The degree of leu kocyte infiltration and connective tissue destruction in gingiva from GAgP patients was not distinctly different from that in gingiva from AP. The gin gival specimens with heavy PMN infiltration from both GAgP and AP patients presented strong expressions of IL-1 beta and TNF-alpha; showed more extens ive inflammatory cell infiltration; had severe connective tissue destructio n; and presented severe elongation and ulceration of pocket epithelium. In gingiva from healthy subjects, inflammation was minor with visually no PMN, CD68(+), or the positive cells of IL-8, ICAM-1, IL-1 beta and TNF-alpha ex pression. Conclusions: Enhanced accumulation of PMN, which is associated with the upr egulation of IL-8, ICAM-1, IL-1 beta, and TNF-alpha expression, relates to the severity and activity of GAgP. In addition to macrophages, PMN and/or e pithelial cells might also be important sources of IL-8, IL-1 beta, and TNF -alpha production in gingiva.