Dietary zinc alters early inflammatory responses during cutaneous wound healing in weanling CD-1 mice

Zinc deficiency is a well-known health problem associated with delayed wound healing, yet the precise mechanisms that underlie the delay remain unknown. We hypothesized that zinc deficiency delays wound healing as a result of decreased nuclear factor (NF)κB activation, reduced expression of proinflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α], and a decrease in neutrophil infiltration during the early stage of cutaneous wound healing. We used a cutaneous, full-thickness excisional wound model in CD-1 mice to examine the rate of wound closure as well as mRNA levels of inhibitory (I)κBα, IL-1β, and TNF-α and infiltration of neutrophils at the wound site of mice fed a diet containing <1 (deficient), 50 (control), 500, or 1000 μg zinc/g diet. Zinc deficiency reduced the rate of wound closure and mRNA levels of IL-1β and TNF-a and attenuated infiltration of neutrophils at the wound site compared with controls. Interestingly, zinc supplementation at 1000 μg/g delayed the rate of wound closure and decreased mRNA levels of TNF-a and infiltration of neutrophils compared with mice fed the control diet. These findings demonstrate that zinc deficiency and high-dose zinc supplementation delay wound healing as a result of altered inflammatory responses and suggest that adequate zinc supplementation may have beneficial effects on the inflammatory responses to enhance cutaneous wound healing.