Lack of interferon-gamma production despite the presence of interleukin-18during cutaneous wound healing

Background: Recently, we have reported a rapid and strong induction of inte rleukin-18 (IL-18) upon cutaneous injury in mice. In this paper, we investi gated a possible role of IL-18 in triggering interferon-gamma (IFN-gamma) p roduction at the wound site. Materials and Methods: Expression of IFN-gamma during cutaneous wound heali ng was analyzed by RNase protection assay, Western blot, ELISA, and immunoh istochemical techniques in a murine model of excisional skin repair. Results: We could not detect any IFN-gamma mRNA and protein expression duri ng normal skin repair. Additionally, impaired healing in the genetically di abetic db/db mouse, which was used as a model for a prolonged inflammatory phase of repair, was characterized by largely elevated levels of IL-18 duri ng the late phase of repair and an absence of IFN-gamma. Western blot analy sis for T-cell- and monocyte/macrophage-specific marker proteins (CD4, F4/8 0) clearly revealed the presence of these subsets of leukocytic cells at th e wound site, that are known to produce IFN-gamma in response to IL-18. Fur thermore, we provide evidence that the presence of transforming growth fact or-beta1 (TGF-beta1) at the wound site might reflect a counterregulatory me chanism in IL-18-induced IFN-gamma production, as TGF-P I strongly suppress ed IL-18/phytohaemagglutinin (PHA)-induced IFN-gamma production by peripher al blood mononuclear cells (PBMC) in vitro. Conclusions: Normal tissue regeneration processes after cutaneous injury we re not dependent on the presence of IFN-gamma in vivo, and IL-18 must serve additional roles rather than inducing IFN-gamma during the healing process .