Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu

Cytokine Growth Factor Rev. 2001 Mar;12(1):53-72. doi: 10.1016/s1359-6101(00)00015-0.


IL-18 is a potent proinflammatory cytokine able to induce IFNgamma, GM-CSF, TNFalpha and IL-1 in immunocompetent cells, to activate killing by lymphocytes, and to up-regulate the expression of certain chemokine receptors. IL-18 is also essential to host defences against severe infections. In particular, the clearance of intracellular bacteria, fungi and protozoa requires the induction of host-derived IFNgamma, which evokes effector molecules such as nitric oxide. Also, IL-18 plays a part in the clearance of viruses, partly by the induction of cytotoxic T cells, and the expulsion of viruses is impaired in IL-18-deficient mice. IL-18 also enhances tumour rejection by its potent capacity to augment the cytotoxic activity of NK and T cells in vivo. In contrast, recent studies also demonstrate a convincing role for IL-18 in atopic responses, including atopic asthma. IL-18 induces naive T cells to develop into Th2 cells. Moreover, IL-18 also induces IL-13 and/or IL-4 production by NK cells, mast cells and basophils. Therefore, IL-18 should be seen as a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / physiopathology
  • Crohn Disease / immunology
  • Crohn Disease / physiopathology
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Gene Expression Regulation
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / physiopathology
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-12 / pharmacology
  • Interleukin-18 / chemistry
  • Interleukin-18 / pharmacology
  • Interleukin-18 / physiology*
  • Interleukin-18 Receptor alpha Subunit
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Liver Diseases / immunology
  • Liver Diseases / physiopathology
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / physiopathology
  • Receptors, Interleukin / chemistry
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-18
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism


  • IL18R1 protein, human
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Interleukin-12
  • Interferon-gamma