High Dietary Salt Exposure During Sensitization Is Associated with Increased Severity of Allergic Contact Dermatitis in Mice

Background: High dietary salt intake has been implicated in immune-mediated inflammatory diseases; however, its impact on allergic contact dermatitis (ACD) remains unclear. This study examined whether dietary salt exposure during the sensitization phase influences the severity of DNFB-induced ACD in mice. Methods: Female C57BL/6N mice were fed a normal diet (ND) or an 8% high-salt diet (HSD). In a subset, salt intake was normalized prior to sensitization (HSD → ND). ACD was induced using a DNFB sensitization and challenge protocol. Ear swelling was quantified using incremental area under the curve (iAUC). Histological analyses and measurements of plasma and skin sodium were performed. Results: HSD-fed mice showed greater ear swelling and higher iAUC than ND controls, accompanied by enhanced inflammatory cell infiltration. Skin sodium concentration differed among groups, with a higher concentration in HSD-fed mice compared that in the HSD → ND group. Normalization of salt intake prior to sensitization attenuated disease severity. Spearman analyses indicated that total sodium intake and plasma potassium concentration were associated with inflammatory severity. Conclusions: Dietary salt exposure during immune sensitization exacerbated experimental ACD and was associated with systemic electrolyte alterations. These findings suggest that sodium exposure during immune activation may influence allergic skin inflammation.