Dimethyl Fumarate Ameliorates Delayed Wound Healing Due to IL-36Ra Deficiency Through Inhibition of NET Formation and Oxidative Stress

The study examined the effect of dimethyl fumarate (DMF), an immune modulator and inducer of the antioxidant response, on delayed wound healing in mice deficient in IL-36 receptor antagonist (Il36rn-/- mice). Full-thickness excisional wounds were produced on the mice and healing was assessed. The administration of DMF accelerated wound healing in Il36rn-/- mice at 3 and 7 days after injury. It also decreased the number of infiltrated neutrophils and macrophages, skin expression of TGF-β and IL-1β, and neutrophil extracellular trap (NET) formation. In vitro experiments showed that the addition of NETs to macrophages enhanced the expression of oxidative stress, which was suppressed by DMF. The study concluded that DMF ameliorates delayed wound healing due to IL-36 receptor antagonist deficiency through suppression of NET formation and oxidative stress.