Blocking Proinflammatory Cytokine Release Modulates Peripheral Blood Mononuclear Cell Response to Porphyromonas gingivalis

Abstract

Background Chronic periodontitis is an inflammatory disease in which cytokines play a major role in the progression of disease. Anti-inflammatory cytokines (IL-4 and IL-10) were reported to be absent or reduced in diseased periodontal tissues, suggesting an imbalance between the pro- and anti-inflammatory mediators. We have tested the hypothesis that there is cellular cross-talk mediated by pro- and anti-inflammatory cytokines and that blocking pro-inflammatory cytokine (TNF-α and IL-1) production will enhance anti-inflammatory cytokine (IL-4 and IL-10) production from peripheral blood mononuclear cells (PBMC) in response to P. gingivalis. Methods PBMC were isolated from individuals diagnosed with chronic periodontitis 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 was used as the bacterial stimulants. TNF-α and IL-1 production was neutralized by specific antibodies against TNF-α and IL-1α or β. Culture supernatants were evaluated by ELISA 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 while heat-killed P. gingivalis led to a significant increase in IL-10 levels compared to unstimulated or live P. gingivalis-stimulated cells from both healthy and periodontitis individuals. Overall, PBMC from patients with chronic periodontitis produced significantly lower IL-10 in response to ConA and P. gingivalis suggesting chronic suppression of the anti-inflammatory cytokine production. Blocking the pro-inflammatory cytokine response did not result in any substantial change in IL-10 or IL-4 response to live P. gingivalis. Blocking the pro-inflammatory cytokine response restored IL-10 production by cells from chronic periodontitis in response to P. gingivalis LPS. Conclusion These findings suggest that PBMC from patients with chronic periodontitis have suppressed anti-inflammatory cytokine production that can, in part, be restored by neutralizing pro-inflammatory cytokines. Monocytes are an important source of IL-10 production and monocyte-derived IL-10 might play a regulatory role in the pathogenesis of chronic periodontitis.

Peripheral T helper cell profiles during management of periodontitis

“…ConA stimulation of PBMCs elicited greater cytokine production compared to PBMCs alone in line with previous studies (Berker et al, 2013;Fujihashi et al, 1993;Gonçalves et al, 2013;McFarlane et al, 1990). Upon P. gingivalis stimulation, IL-10 was the most abundant cytokine produced with 3.5-fold and seven-fold higher mean concentration than IFN-γ at health and baseline, respectively.…”

Association between Periodontal Health Status and Cognitive Abilitie s. The Role of Cytokine Profile and Systemic Inflammation

“…It was presented earlier that PBMCs from patients with chronic periodontitis have suppressed anti-inflammatory cytokine production (IL-10) [ 42 ] and that the IL-10 production was restored after blocking the pro-inflammatory cytokine release by peripheral blood mononuclear cells (PBMC) from chronic periodontitis patients in response to P. gingivalis LPS. We showed an increase in IL-10 production by PBL, therefore it seems that the cytokine profile, as well as the inflammatory state associated with the presence of both periodontitis and cognitive impairment, change the leukocyte response, which replay with the increased production of both pro and anti-inflammatory cytokines.…”

Leptomeningeal Cells Transduce Peripheral Macrophages Inflammatory Signal to Microglia in Reponse toPorphyromonas gingivalisLPS

“…Among the common chronic inflammatory disorders in adults, much attention has been paid to the periodontitis as the pathogenesis of CNS disorders, including AD [13, 15, 44]. The increase in macrophage-derived TNF- α and IL-1 β in the circulation during periodontitis [39, 40] also supports the idea that chronic periodontitis is involved in the pathogenesis of systemic inflammatory diseases, including atherosclerosis, cardiovascular disease, and diabetes [10–12]. Therefore, it is reasonable to consider that the increased M1 polarization of macrophages during chronic periodontitis can be also a risk factor for AD, because the elevated levels of TNF- α and IL1- β are associated not only with the cognitive decline but also with the progression of AD [45–47].…”