Mechanisms of epithelial thickening due to IL-1 signalling blockade and TNF-α administration differ during wound repair and regeneration

IL-1 and TNF-α are always present during wound repair, but their pleiotropic and synergistic effects are incompletely understood. In this work, we evaluated the role of IL-1 in wound repair, and examined whether TNF-α administration impaired scarless wound repair. First, we characterised wound repair in outbred CD-1 mice according to age and sex in an ear punch wound model. Then, we examined the effects of Interleukin 1 receptor antagonist (IL-1ra) and TNF-α placement inside ear wounds by means of loaded Heparin beads in young and middle-aged male and female mice. Wounds in middle-aged females repaired with scarless characteristics, whereas those in young males showed fibrotic scarring. Rather than improving wound repair in young males, IL-1 signalling blockade increased epithelial thickness and IL-1β and TNF-α expression, and diminished epidermal apoptosis. TNF-α impaired wound repair in middle-aged females, which exhibited acanthosis and overexpression of IL-1, but no change in apoptosis. These findings suggest that this mechanism of epidermal thickening differs from that observed in IL1-ra–treated animals.