Regulation of interferon-gamma production by IL-12 and IL-18

Curr Opin Immunol. 1998 Jun;10(3):259-64. doi: 10.1016/s0952-7915(98)80163-5.

Abstract

IL-18 (interferon-inducing factor) and IL-12 exhibit a marked synergism in interferon-gamma induction in T cells. Investigations into the mechanism of this synergism have revealed that IL-12 upregulates expression of the IL-18 receptor on cells producing interferon-gamma. Although IL-18 does not induce the development of Th1 cells, it is essential for the effective induction and activation of Th1 cells by IL-12. As for natural killer cells, IL-18 seems to activate them independently of IL-12. Although IL-12 and IL-18 activate both innate and acquired immunity, their excessive production by activated macrophages may induce multiple organ disorders including disruption of the immune system.

Publication types

  • Review

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Cells, Cultured
  • Cytokines / pharmacology*
  • Cytokines / physiology
  • Cytokines / toxicity
  • Drug Synergism
  • Gene Expression Regulation / drug effects*
  • Immunoglobulin E / biosynthesis
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Interleukin-12 / pharmacology*
  • Interleukin-12 / physiology
  • Interleukin-12 / toxicity
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / metabolism
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Models, Immunological
  • RNA, Messenger / biosynthesis
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-18
  • Signal Transduction
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Up-Regulation / drug effects

Substances

  • Cytokines
  • Il18r1 protein, mouse
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Interleukin-12
  • Immunoglobulin E
  • Interferon-gamma