Neural regulation of the immune system modulates hypertension-induced target-organ damage

Shown is the neural circuitry of the inflammatory reflex.⁹ The inflammatory reflex controls innate immune responses by a mechanism that targets the regulatory transcription factor nuclear factor-κB (NF-κB). Exogenous and endogenous molecular products of infection and injury interact with receptors that are expressed by cells of the innate immune system, including Toll-like receptors (TLRs) and nucleotide-binding domain (NLRs). Ligand–receptor interactions activate innate immune responses and induce the secretion of pro-inflammatory cytokines. These molecules also activate afferent sensory neurons, which constitute the sensory arc of the inflammatory reflex. Axons travelling in the vagus nerve relay this information as action potentials to the brain stem. This interconnection in turn activates the efferent arc, which is known as the cholinergic anti-inflammatory pathway. Subsequent signaling inhibits innate immune responses in the spleen through inhibitory signals that arise in the brain stem, traverse the vagus nerve and signal through nicotinic acetylcholine receptor subunit α7 (α7nAChR), which is expressed by cytokine-producing immune cells. This leads to the suppression of NF-κB activation and the inhibition of innate immune responses. The inflammatory reflex could be initiated by many possible ligands through key receptors of the innate immune control. A multifactorial process is clearly involved.