Cutting edge: IL-18-transgenic mice: in vivo evidence of a broad role for IL-18 in modulating immune function

J Immunol. 2001 Jun 15;166(12):7014-8. doi: 10.4049/jimmunol.166.12.7014.

Abstract

IL-18 has been shown to be a strong cofactor for Th1 T cell development. However, we previously demonstrated that when IL-18 was combined with IL-2, there was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells. More recently, we and other groups have reported that IL-18 can potentially induce IgE, IgG1, and Th2 cytokine production in murine experimental models. Here, we report on the generation of IL-18-transgenic (Tg) mice in which mature mouse IL-18 cDNA was expressed. CD8+CD44high T cells and macrophages were increased, but B cells were decreased in these mice while serum IgE, IgG1, IL-4, and IFN-gamma levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-gamma, IL-4, IL-5, and IL-13 than control wild-type mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.

MeSH terms

  • Adjuvants, Immunologic / biosynthesis
  • Adjuvants, Immunologic / genetics*
  • Adjuvants, Immunologic / physiology*
  • Animals
  • B-Lymphocytes / cytology
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • Cell Count
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Gene Expression Regulation / immunology
  • Growth Inhibitors / genetics
  • Growth Inhibitors / physiology
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / blood
  • Interleukin-13 / biosynthesis
  • Interleukin-18 / biosynthesis
  • Interleukin-18 / genetics*
  • Interleukin-18 / physiology*
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / blood
  • Interleukin-5 / biosynthesis
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Macrophages / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / immunology*
  • Spleen / cytology
  • Transgenes / immunology*
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • Adjuvants, Immunologic
  • Growth Inhibitors
  • Immunoglobulin G
  • Interleukin-13
  • Interleukin-18
  • Interleukin-5
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma