Attenuation of inflammatory cytokines with invasive vagus nerve stimulation in the skin of mouse models of psoriasis and eczema

Summary: Abstract Body: The cholinergic anti-inflammatory pathway, activated through vagus nerve stimulation (VNS), plays a crucial role in immune response regulation. Although the skin lacks direct vagal innervation, we hypothesized that vagal modulation of systemic inflammation might influence cutaneous inflammatory disorders. We investigated this possibility using two mouse models: C57/BL6 mouse with imiquimod-induced psoriasis-like lesions and NC/Nga mouse with dinitrochlorobenzene (DNCB)-induced eczematous dermatitis. Left vagus nerve stimulation (5V/5mA/5Hz/5ms/5min) was applied at 6 and 24 hours pre-sacrifice in the imiquimod model, and 24 hours pre-sacrifice in the DNCB model. In both models, VNS significantly reduced epidermal thickening, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and CD11b-positive macrophage infiltration in the skin. Immunofluorescence staining revealed decreased TNF-α response in the epidermis after VNS. In DNCB-treated mice, a single VNS application reduced plasma TNF-α levels by 32% (p<0.01). Notably, protein levels of TNF-α and IL-1β in the spleen were elevated in both models and downregulated by VNS, suggesting that local dermatitis may be linked to systemic inflammation. VNS treatment reduced inflammatory markers in both splenic tissue and plasma, indicating its therapeutic effects may be mediated through modulation of systemic inflammation. These findings establish VNS as a potential therapeutic approach for inflammatory skin diseases and provide mechanistic insights into its anti-inflammatory effects in cutaneous tissue. William J. Nahm¹, Ki-Joong Kim⁴, Eui Namgung⁵, John Koo², Vincent Falanga³ 1. New York University Grossman School of Medicine, New York, NY, United States. 2. Psoriasis and Skin Treatment Center, University of California San Francisco School of Medicine, San Francisco, CA, United States. 3. Dept. of Dermatology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States. 4. Dept. of Korean Medicine, Daejeon University, Daejeon, Daejeon, Korea (the Republic of). 5. Dept. of Physics, University of California San Diego, La Jolla, CA, United States. Translational Studies: Preclinical