Acetylcholine and the alpha 7 nicotinic receptor: a potential therapeutic target for the treatment of periodontal disease?

Objectives: The aim of this review is to examine the evidence for a functional cholinergic system operating within the periodontium and determine the evidence for its role in periodontal immunity.

Introduction: Acetylcholine can influence the immune system via the 'cholinergic anti-inflammatory pathway'. This pathway is mediated by the vagus nerve which releases acetylcholine to interact with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) on proximate immuno-regulatory cells. Activation of the α7nAChR on these cells leads to down-regulated expression of pro-inflammatory mediators and thus regulates localised inflammatory responses. The role of the vagus nerve in periodontal pathophysiology is currently unknown. However, non-neuronal cells can also release acetylcholine and express the α7nAChR; these include keratinocytes, fibroblasts, T cells, B cells and macrophages. Therefore, by both autocrine and paracrine methods non-neuronal acetylcholine can also be hypothesised to modulate the localised immune response.

Methods: A Pubmed database search was performed for studies providing evidence for a functional cholinergic system operating in the periodontium. In addition, literature on the role of the 'cholinergic anti-inflammatory pathway' in modulating the immune response was extrapolated to hypothesise that similar mechanisms of immune regulation occur within the periodontium.

Conclusion: The evidence suggests a functional non-neuronal 'cholinergic anti-inflammatory pathway' may operate in the periodontium and that this may be targeted therapeutically to treat periodontal disease.