Vagus Nerve Stimulation Reduces Cutaneous Inflammation and Proinflammatory Cytokines in Murine Models of Psoriasis...

Vagus nerve stimulation (VNS) modulates systemic inflammation through the cholinergic anti-inflammatory pathway, but its effects on cutaneous inflammatory diseases remain unexplored. We investigated whether invasive VNS could reduce clinical inflammation and proinflammatory cytokines in murine models of psoriasis and atopic dermatitis (AD). C57BL/6 mice received imiquimod 5% cream to induce psoriasiform inflammation, while NC/Nga mice received 2,4-dinitrochlorobenzene (DNCB) to induce AD-like inflammation. Acute invasive VNS (5 Hz/5 ms for 5 min) or sham procedures were performed 6 or 24 h before sacrifice. Cutaneous cytokine levels were assessed by immunoblotting and immunofluorescence staining, while systemic inflammation was evaluated by analyzing splenic and plasma cytokines. VNS reduced TNF-α and IL-6 in imiquimod-treated skin at both 6- and 24-h post-stimulation (TNF-α/6 h: 63%, p < 0.01; IL-6/6 h: 63%, p < 0.01; TNF-α/24 h: 69%, p < 0.001; IL-6/24 h: 60%, p < 0.05). In DNCB-treated skin, VNS decreased TNF-α, IL-1β, and IL-6 at 24 h post-stimulation (TNF-α/24 h: 68%, p < 0.001; IL-1β/24 h: 48%, p < 0.05; IL-6/24 h: 66%, p < 0.01). VNS altered cutaneous CD11b-positive macrophage distribution patterns and reduced splenic cytokine levels (TNF-α and IL-1β) in the psoriasis model (TNF-α/6 h: 73%, p < 0.001; 24 h: 46%, p < 0.05) (IL-1β/6 h: 48%, p < 0.01; 24 h: 41%, p < 0.05) while plasma TNF-α decreased in the AD model (24 h: 32%, p < 0.01). This study provides the first evidence that VNS reduces proinflammatory cytokines in inflammatory skin diseases, supporting clinical translation for dermatological applications.