Interleukin-18 regulates both Th1 and Th2 responses

Annu Rev Immunol. 2001;19:423-74. doi: 10.1146/annurev.immunol.19.1.423.

Abstract

Although interleukin-18 is structurally homologous to IL-1 and its receptor belongs to the IL-1R/Toll-like receptor (TLR) superfamily, its function is quite different from that of IL-1. IL-18 is produced not only by types of immune cells but also by non-immune cells. In collaboration with IL-12, IL-18 stimulates Th1-mediated immune responses, which play a critical role in the host defense against infection with intracellular microbes through the induction of IFN-gamma. However, the overproduction of IL-12 and IL-18 induces severe inflammatory disorders, suggesting that IL-18 is a potent proinflammatory cytokine that has pathophysiological roles in several inflammatory conditions. IL-18 mRNA is expressed in a wide range of cells including Kupffer cells, macrophages, T cells, B cells, dendritic cells, osteoblasts, keratinocytes, astrocytes, and microglia. Thus, the pathophysiological role of IL-18 has been extensively tested in the organs that contain these cells. Somewhat surprisingly, IL-18 alone can stimulate Th2 cytokine production as well as allergic inflammation. Therefore, the functions of IL-18 in vivo are very heterogeneous and complicated. In principle, IL-18 enhances the IL-12-driven Th1 immune responses, but it can also stimulate Th2 immune responses in the absence of IL-12.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Cell Differentiation / drug effects
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypersensitivity / immunology
  • Infections / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-12 / physiology
  • Interleukin-18 / biosynthesis
  • Interleukin-18 / chemistry
  • Interleukin-18 / genetics
  • Interleukin-18 / pharmacology
  • Interleukin-18 / physiology*
  • Interleukin-18 Receptor alpha Subunit
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Models, Immunological
  • Multigene Family
  • Organ Specificity
  • Protein Precursors / metabolism
  • Receptors, Interleukin / chemistry
  • Receptors, Interleukin / drug effects
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / physiology
  • Receptors, Interleukin-18
  • Signal Transduction
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • Cytokines
  • IL18R1 protein, human
  • Il18r1 protein, mouse
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Protein Precursors
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Interleukin-12
  • Interferon-gamma