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

Mol Med. 2000 Dec;6(12):1016-27.

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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • DNA, Complementary / metabolism
  • Diabetes Mellitus, Experimental
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunohistochemistry
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / metabolism
  • Interleukin-18 / genetics*
  • Interleukin-18 / metabolism*
  • Lymphocytes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mutation
  • Phenotype
  • Promoter Regions, Genetic
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Ribonucleases / metabolism
  • Skin / metabolism*
  • Skin / pathology*
  • Time Factors
  • Tissue Distribution
  • Up-Regulation
  • Wound Healing*

Substances

  • DNA, Complementary
  • Interleukin-18
  • RNA, Messenger
  • RNA
  • Interferon-gamma
  • Ribonucleases