title: Blocking proinflammatory cytokine release modulates peripheral blood mononuclear cell response to Porphyromonas gingivalis.
abstract: BACKGROUND
  Chronic periodontitis (CP) is an inflammatory disease in which cytokines play a major role in the progression of disease. Anti-inflammatory cytokines (interleukin 4 [IL-4] and IL-10) were reported to be absent or reduced in diseased periodontal tissues, suggesting an imbalance between the proinflammatory and anti-inflammatory mediators. This study tests the hypothesis that there is cellular crosstalk mediated by proinflammatory and anti-inflammatory cytokines and that blocking proinflammatory cytokine (tumor necrosis factor-α [TNF-α] and IL-1) production will enhance anti-inflammatory cytokine (IL-4 and IL-10) production from peripheral blood mononuclear cells (PBMCs) in response to Porphyromonas gingivalis.
  
  
  METHODS
  PBMCs were isolated from individuals diagnosed with CP or healthy individuals and cultured for 24 hours. Concanavalin A (ConA) was used as an activator of lymphocyte function. Live and heat-killed P. gingivalis or lipopolysaccharide from P. gingivalis were used as the bacterial stimulants. TNF-α and IL-1 production was neutralized by specific antibodies against TNF-α and IL-1α or IL-β. Culture supernatants were evaluated by enzyme-linked immunosorbent assay for TNF-α, IL-1β, IL-4, and IL-10 production.
  
  
  RESULTS
  Live P. gingivalis did not result in any significant IL-10 or IL-4 release, whereas heat-killed P. gingivalis led to a significant increase in IL-10 levels compared with unstimulated or live P. gingivalis-stimulated cells from both healthy individuals or those with CP. Overall, PBMCs from patients with CP produced significantly lower IL-10 in response to ConA and P. gingivalis, suggesting chronic suppression of the anti-inflammatory cytokine production. Blocking the proinflammatory cytokine response did not result in any substantial change in IL-10 or IL-4 response to live P. gingivalis. Blocking the proinflammatory cytokine response restored IL-10 production by cells from CP in response to P. gingivalis lipopolysaccharide.
  
  
  CONCLUSIONS
  These findings suggest that PBMCs from patients with CP have suppressed anti-inflammatory cytokine production that can, in part, be restored by neutralizing proinflammatory cytokines. Monocytes are an important source of IL-10 production, and monocyte-derived IL-10 might play a regulatory role in the pathogenesis of CP.
authors.affiliation: Department of Periodontology, Faculty of Dentistry, University of Hacettepe, Ankara, Turkey.
authors.forename: Ezel
authors.initials: E
authors.lastname: Berker
authors.forename: Alpdogan
authors.initials: A
authors.lastname: Kantarci
authors.forename: Hatice
authors.initials: H
authors.lastname: Hasturk
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000276:immunology / Q000382:microbiology; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; C508598:IL4 protein, human; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4