Counterregulation of interleukin-18 mRNA and protein expression during cutaneous wound repair in mice

Recent work has suggested interleukin-18 to represent a proinflammatory cyt okine that contributes to systemic and local inflammation. As the process o f cutaneous wound healing crucially involves an inflammatory phase of repai r, we investigated the regulation of interleukin-18 during the repair proce ss. In non-wounded skin we observed high levels of interleukin-18 mRNA, whe reas corresponding interleukin-18 protein was expressed only at low basal l evels. Upon injury, we found a rapid and large induction of interleukin-18 protein expression, which is directly correlated with decreasing mRNA. leve ls within the wound. Immunohistochemical analysis revealed different sites of expression in the wounded area, with keratinocytes as one major source o f interleukin-18 production. The counterregulation of interleukin-18 mRNA a nd protein expression during wound repair in vivo might represent a general mechanism for interleukin-18 expressional regulation, as cytokine-stimulat ed keratinocytes exhibit a similar downregulation of interleukin-18 mRNA th at is directly associated with increasing interleukin-18 protein levels in vitro. The rapid induction of interleukin-18 during wound healing suggests a role for interleukin-18 within the early phase of repair rather than a ro le in costimulation of interferon-gamma release fi om T cells, which are pr esent in high numbers within the wounded area only during the late inflamma tory phase of repair.