Pirfenidone Ointment Modulates the Burn Wound Bed in C57BL/6 Mice by Suppressing Inflammatory Responses

An inflammatory response is the normal response to a burn-induced injury. The burn-associated inflammation can lead to further tissue damage as the tissue tries to repair the damage. Prolonged or excessive inflammation is associated with increased fibrosis of burn wounds and the development of hypertrophic scars. The high incidence of hypertrophic scar formation is one of the many challenges to treating deep partial-thickness burns. Prophylactic treatment to improve burn-induced hypertrophic scarring is lacking. For this reason, we evaluated prophylactic treatment of deep partial-thickness burns with pirfenidone in C57BL/6 mice. Pirfenidone is an FDA-approved anti-fibrotic drug for systemic use in the treatment of idiopathic lung fibrosis and other fibrotic disorders. Additionally, pirfenidone has anti-inflammatory activity. We tested treatment efficacy of pirfenidone using a mouse model of deep partial-thickness burns. Inflammatory cytokines including IL-1, IL-2, IL-6, IL-13, G-CSF, and MIP-1, along with neutrophil infiltration, were significantly reduced in wounds when mice were treated during the inflammatory phase of burn wound healing. Additionally, pirfenidone significantly reduced expression of SMA 12days after the induction of burns and modestly reduced hydroxyproline in 22-day-old burn wounds. Results show that pirfenidone treatment modulated the inflammatory response of the burn wound. The findings in this study indicate that further examination is required to validate the use of pirfenidone for prophylactic treatment to improve long-term outcomes of scarring and contracture in deep partial-thickness burn wounds.