In mouse studies, the anti‑worm drug niclosamide, when applied to the skin, reduced inflammation in two common skin problems – psoriasis‑like lesions caused by imiquimod and rosacea‑like lesions triggered by the peptide LL‑37. It worked by lowering the activity of the inflammatory STAT3 pathway and by shifting immune cells away from a pro‑inflammatory state (IL‑17‑producing T cells) toward more regulatory T cells that calm the immune response.

Niclosamide is an oral anthelmintic agent and was reported to also have anti-inflammatory effects by suppressing STAT3 signaling pathways. In this study, we investigated the effect of niclosamide on skin inflammatory diseases to determine its potential as a therapeutic drug. We investigated the effects of niclosamide on two models of skin inflammatory diseases: imiquimod -induced psoriasis-like skin inflammation and LL-37-induced rosacea mouse models. Our experimental results showed that niclosamide ameliorated the psoriasis-like skin inflammation and reduced proinflammatory cytokine production in the psoriasis mouse model. Moreover, niclosamide restored the imbalance between IL-17-expressing γδT cells and Tregs in the psoriasis model. Topical application of niclosamide significantly decreased the abundance of IL-17A⁺ γδT cells, which was increased by imiquimod. Moreover, niclosamide significantly increased the abundance of CD4⁺Foxp3⁺ Tregs. In the LL-37-induced rosacea mouse model, niclosamide significantly reduced the number of inflammatory cells including neutrophils and mast cells that play major roles in initiating inflammation and inducing uncontrolled dermal vessel function in rosacea. Lastly, niclosamide significantly reduced the number of p-STAT3-positive cells in mouse skin, which was increased by treatment with imiquimod or LL-37. We found an anti-inflammatory effect of niclosamide in psoriasis and rosacea mouse models and demonstrated the ability of niclosamide in controlling skin inflammation by recalibrating T cell differentiation and restoring T cell regulatory function. Niclosamide, as a STAT3 inhibitor, is a promising therapeutic for skin inflammation, particularly for preventing the relapse of disease by restoring regulatory cell functions.