title: Are cytokines linked to collagen breakdown during periodontal disease progression?
abstract: BACKGROUND
  Evidence of the role of cytokines produced by resident and inflammatory cells during inflammation is well established. The aim of this study was to quantify in healthy and diseased human gingiva the area fraction (AA%) occupied by collagen fibers and the amount of cytokines such as interleukin (IL)-1beta, IL-4, IL-6, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and epidermal growth factor (EGF) to investigate a possible correlation between such cytokines, collagen degradation, and the gingival index.
  
  
  METHODS
  Gingival tissue specimens from 6 healthy controls (group 1), 6 patients with mild gingival inflammation (group 2), 6 patients with moderate gingival inflammation (group 3), and 6 patients with severe gingival inflammation (group 4) were cultured for 72 hours, and the cytokines present in the culture media were quantified using an enzyme-linked immunosorbent assay (ELISA). Paraffin gingival sections from the 24 subjects were stained with sirius red F3Ba for visualization of collagen fibers, then the area fraction (AA%) occupied by the gingival fibers was determined by automated image analysis.
  
  
  RESULTS
  The present study revealed significant differences (P < 0.05) between means of AA% in group 1 (53%), group 2 (41%), group 3 (39.5%), and group 4 (35%) for collagen fibers. Compared to controls, there were significant increases of IL-1beta (groups 3 and 4), IL-6, and TNF-alpha (group 3); a significant decrease of IL-4 (groups 2, 3, and 4) and TGF-beta (groups-2 and, 3); and no change of EGF. The collagen AA% was significantly correlated with the amounts of IL-4 and TGF-beta, and significantly inversely correlated with the amounts of IL-1beta for all 3 inflamed groups and IL-6 and TNF-alpha for groups 2 and 3.
  
  
  CONCLUSIONS
  The present study showed that EGF was not changed in inflamed gingival tissue and that IL-1beta and IL-4 were particularly and intensively correlated with collagen loss. These 2 cytokines could be markers of clinical severity during active periodontitis.
authors.affiliation: Department of Non-Mineralized Tissue Physiopathology, Faculty of Dental Surgery, Université René Descartes Paris V, Montrouge, France. godeau_g@yahoo.fr
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Ejeil
authors.forename: Frederick
authors.initials: F
authors.lastname: Gaultier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Igondjo-Tchen
authors.forename: Karim
authors.initials: K
authors.lastname: Senni
authors.forename: Bernard
authors.initials: B
authors.lastname: Pellat
authors.forename: Gaston
authors.initials: G
authors.lastname: Godeau
authors.forename: Bruno
authors.initials: B
authors.lastname: Gogly
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D002648:Child; D046508:Culture Techniques; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000378:metabolism; D024022:Fibrillar Collagens / Q000378:metabolism*; D005891:Gingivitis / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D010512:Periodontal Index; D010518:Periodontitis / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D024022:Fibrillar Collagens; D007378:Interleukins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor