Figure 1.

The central nervous system (CNS) mediates the release of various immune influencing glucocorticoids via activation of a series of connected regions within the brain referred to as the hypothalamic–pituitary–adrenal axis. Research suggests the CNS to be primarily immune-suppressive in action, inhibiting production of pro-inflammatory cytokines, chemotactic factors and limiting migration and activation in several immune cell types.^111–114 Additionally the CNS elicits differential immune effects dependent on cell type and stage of development, inducing the expansion and migration of immature dendritic cells while seemingly promoting a tolerogenic phenotype in their mature counterparts.^113,115 Although less studied, several papers have demonstrated that the sympathetic nervous system is able to modulate immune activity through production of epinephrine and norepinephrine promoting a T helper type 2 (Th2) and Th17 phenotype in in T cells and dendritic cells, respectively.^116,117 Produced by the parasympathetic nervous system, acetylcholine has been shown to interact directly with multiple immune cell subsets through expression of acetylcholine receptors, leading to suppression of a number of pro-inflammatory pathways in macrophages and other immune cells.^118–120 Abbreviations: IFN-γ, interferon-γ; IL-17, interleukin-17; NF-κB, nuclear factor-κB; STAT, signal transducer and activator of transcription; Th1, T helper type 1; TNF, tumour necrosis factor.