Abstract
The stress response and relevant stress systems serve as a potential mechanism for linking inflammation with disease outcomes. Regulation of inflammation by the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) has been studied, but little is known about how the parasympathetic nervous system (PNS) mediates immunity. This research aimed to confirm the PNS as anti-inflammatory by measuring cytokine (TNF, IL-6, IL-1β, and IL-10) levels in LPS-stimulated blood incubated with increasing concentrations of acetylcholine (ACh), the primary PNS neurotransmitter. It also sought to determine whether acute stress affected ACh sensitivity of cytokine production. In both stressed (n = 4) and unstressed (n = 5) young adults, ACh was found to dose-dependently inhibit production of pro-inflammatory cytokines TNF and IL-6, but not IL-1β nor the anti-inflammatory IL-10. Acute stress,\r v\r evoked by the established Trier Social Stress Test, did not significantly modulate ACh sensitivity of cytokine production. However, data suggested an effect of stress to increase ACh inhibition of TNF and IL-6, and the reverse effect for IL-10 and IL-1β. Lack of significance was attributed to small sample size and inter-individual variability in stress response patterns. The cholinergic anti-inflammatory pathway identified here will prove a crucial target for therapy in the future. Tests of acute stress effects on ACh sensitivity should be replicated in a larger population and compared to stress effects on glucocorticoid (GC) and catecholamine (CAT) sensitivity.