The nervous system and immune system have broad and overlapping
distributions in the body, and interactions of these ubiquitous systems are
central to the field of neuroimmunology. Over the past two decades, there has
been explosive growth in our understanding of neuroanatomical, cellular, and
molecular mechanisms that mediate central modulation of immune functions through
the autonomic nervous system. A major catalyst for growth in this field was the
discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of
the systemic inflammatory response evoked by endotoxin in experimental animals.
This effect was mediated by acetylcholine (ACh) stimulation of nicotinic
receptors on splenic macrophages. Hence, the circuit was dubbed the
“cholinergic anti-inflammatory pathway”. Subsequent work
identified the α7 nicotinic ACh receptor (α7nAChR) as the
crucial target for attenuation of pro-inflammatory cytokine release from
macrophages and dendritic cells. Further investigation made the important
discovery that cholinergic T cells within the spleen and not cholinergic nerve
cells were the source of ACh that stimulated α7 receptors on splenic
macrophages. Given the important role that inflammation plays in numerous
disease processes, cholinergic anti-inflammatory mechanisms are under intensive
investigation from a basic science perspective and in translational studies of
animal models of diseases such as inflammatory bowel disease and rheumatoid
arthritis. This basic work has already fostered several clinical trials
examining the efficacy of VNS and cholinergic therapeutics in human inflammatory
diseases. This review provides an overview of basic and translational aspects of
the cholinergic anti-inflammatory response and relevant pharmacology of drugs
acting at the α7nAChR.