The cholinergic anti-inflammatory pathway: towards innovative treatment of rheumatoid arthritis

The efferent vagus nerve can regulate inflammation via its principal neurotransmitter acetylcholine (ACh), a concept referred to as the 'cholinergic anti-inflammatory pathway'. ACh interacts with members of the nicotinic acetylcholine receptor (nAChR) family, in particular with the alpha7 subunit (alpha7nAChR), which is expressed not only by neurons but also macrophages and other cells involved in the inflammatory response. In these inflammatory cells, the stimulation of alpha7nAChR by ACh and other alpha7nAChR-specific agonists suppresses the release of proinflammatory cytokines. Recent work has suggested that alpha7nAChR could represent a new target for the treatment of rheumatic diseases. In this Perspective, we describe the cholinergic anti-inflammatory pathway and the therapeutic potential of modulating this pathway in rheumatoid arthritis.