Therapeutic Assessment of Topical Pirfenidone in a Murine Model of Imiquimod-induced Psoriasis

Background Psoriasis is a chronic autoimmune skin disease, and the imiquimod (IMQ)-induced mouse model is widely used to assess potential therapeutic interventions. Pirfenidone, known for its anti-fibrotic and anti-inflammatory properties, may offer new treatment opportunities for psoriasis. Purpose This study evaluated the therapeutic efficacy of pirfenidone in IMQ-induced psoriatic lesions in a murine model, with a focus on its anti-inflammatory effects and ability to reduce disease severity. Materials and Methods Female C57BL/6 mice were administered topical IMQ to induce psoriasis-like lesions. Treatment groups received varying doses of pirfenidone or clobetasol (positive control), while disease and vehicle controls were also included. Anti-inflammatory activity was assessed using ex vivo whole blood and splenocyte assays to determine the suppression of lipopolysaccharide-induced tumor necrosis factor alpha (TNF-α) production. TNF-α levels, ear and skin thickness, and histopathological scores were evaluated to measure therapeutic efficacy. Results Pirfenidone inhibited TNF-α production in a concentration-dependent manner. In vitro , effective concentration 50 values were 3.4 µM for whole blood and 5.5 µM for splenocytes. In vivo , pirfenidone treatment led to significant reductions in ear and skin thickening compared to the disease control. Dose-dependent decreases in TNF-α levels were observed in ear and skin tissues, with notable reductions across all tested doses in back skin. Histopathological analysis demonstrated dose-dependent improvement in IMQ-induced pathology scores following pirfenidone administration. Conclusion Pirfenidone exhibits potent anti-inflammatory and therapeutic effects in IMQ-induced murine psoriasis, demonstrating significant reductions in disease severity. These findings support further investigation of pirfenidone as a promising strategy for psoriasis management.