title: Lack of interferon-gamma production despite the presence of interleukin-18 during cutaneous wound healing.
abstract: BACKGROUND
  Recently, we have reported a rapid and strong induction of interleukin-18 (IL-18) upon cutaneous injury in mice. In this paper, we investigated a possible role of IL-18 in triggering interferon-gamma (IFN-gamma) production at the wound site.
  
  
  METHODS
  Expression of IFN-gamma during cutaneous wound healing was analyzed by RNase protection assay, Western blot, ELISA, and immunohistochemical techniques in a murine model of excisional skin repair.
  
  
  RESULTS
  We could not detect any IFN-gamma mRNA and protein expression during normal skin repair. Additionally, impaired healing in the genetically diabetic 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 during the late phase of repair and an absence of IFN-gamma. Western blot analysis for T-cell- and monocyte/macrophage-specific marker proteins (CD4, F4/80) clearly revealed the presence of these subsets of leukocytic cells at the wound site, that are known to produce IFN-gamma in response to IL-18. Furthermore, we provide evidence that the presence of transforming growth factor-beta1 (TGF-beta1) at the wound site might reflect a counterregulatory mechanism in IL-18-induced IFN-gamma production, as TGF-beta1 strongly suppressed IL-18/phytohaemagglutinin (PHA)-induced IFN-gamma production by peripheral blood mononuclear cells (PBMC) in vitro.
  
  
  CONCLUSIONS
  Normal tissue regeneration processes after cutaneous injury were 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.
authors.affiliation: Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kämpfer
authors.forename: J
authors.initials: J
authors.lastname: Paulukat
authors.forename: H
authors.initials: H
authors.lastname: Mühl
authors.forename: C
authors.initials: C
authors.lastname: Wetzler
authors.forename: J
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: S
authors.initials: S
authors.lastname: Frank
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018076:DNA, Complementary / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics* / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D014018:Tissue Distribution; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D018076:DNA, Complementary; D020382:Interleukin-18; D012333:RNA, Messenger; D012313:RNA; D007371:Interferon-gamma; D012260:Ribonucleases