Blocking Proinflammatory Cytokine Release Modulates Peripheral Blood Mononuclear Cell Response to Porphyromonas gingivalis. Issue 9 (1st September 2013)

• Record Type: Journal Article
• Authors: Berker, Ezel; Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E.
• Is Part Of: Journal of periodontology. Volume 84:Issue 9(2013)
• Page Start: 1337
• Page End: 1345
• Publication Date: 2013-09-01
• Subjects: Interleukin‐4 -- interleukin‐10 -- monocytes -- periodontitis -- Porphyromonas gingivalis; Periodontics -- Periodicals; 617.632
• DOI: 10.1902/jop.2012.120422
• Languages: English
• ISSNs: 0022-3492

Abstract

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.