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Gene Review

Il18  -  interleukin 18

Mus musculus

Synonyms: IFN-gamma-inducing factor, IL-1 gamma, IL-18, Igif, Il-18, ...
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Disease relevance of Il18


High impact information on Il18


Chemical compound and disease context of Il18


Biological context of Il18


Anatomical context of Il18


Associations of Il18 with chemical compounds


Physical interactions of Il18


Enzymatic interactions of Il18


Regulatory relationships of Il18


Other interactions of Il18


Analytical, diagnostic and therapeutic context of Il18

  • The inhibitory effect of IL-18 was limited to the early phase of the cocultures, which coincides with proliferation of hemopoietic precursors [21].
  • Lethally irradiated recipients having transplantation with H-2 disparate donor splenocytes demonstrated aGVHD and contained markedly elevated serum levels of IL-18 [3].
  • Hepatic IL-18 expression was up-regulated from 1 to 8 hours after reperfusion [5].
  • Signal transducer and activator of transcription 6 (STAT6) was significantly activated under blockade of IL-18 [5].
  • Administration of anti-IL-18 Abs caused a 100- to 1000-fold increase in bacterial counts in the spleen of infected mice but did not change IFN-gamma production levels [35].


  1. Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. Sugimoto, T., Ishikawa, Y., Yoshimoto, T., Hayashi, N., Fujimoto, J., Nakanishi, K. J. Exp. Med. (2004) [Pubmed]
  2. Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia. Okamoto, M., Kato, S., Oizumi, K., Kinoshita, M., Inoue, Y., Hoshino, K., Akira, S., McKenzie, A.N., Young, H.A., Hoshino, T. Blood (2002) [Pubmed]
  3. Fas ligand-induced caspase-1-dependent accumulation of interleukin-18 in mice with acute graft-versus-host disease. Itoi, H., Fujimori, Y., Tsutsui, H., Matsui, K., Futatsugi, S., Okamura, H., Hara, H., Hada, T., Kakishita, E., Nakanishi, K. Blood (2001) [Pubmed]
  4. Interleukin 18 induces the sequential activation of natural killer cells and cytotoxic T lymphocytes to protect syngeneic mice from transplantation with Meth A sarcoma. Micallef, M.J., Tanimoto, T., Kohno, K., Ikeda, M., Kurimoto, M. Cancer Res. (1997) [Pubmed]
  5. Interleukin 18 causes hepatic ischemia/reperfusion injury by suppressing anti-inflammatory cytokine expression in mice. Takeuchi, D., Yoshidome, H., Kato, A., Ito, H., Kimura, F., Shimizu, H., Ohtsuka, M., Morita, Y., Miyazaki, M. Hepatology (2004) [Pubmed]
  6. T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-gamma and IL-13 production. Hayashi, N., Yoshimoto, T., Izuhara, K., Matsui, K., Tanaka, T., Nakanishi, K. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  7. Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced myocardial injury. Venkatachalam, K., Prabhu, S.D., Reddy, V.S., Boylston, W.H., Valente, A.J., Chandrasekar, B. J. Biol. Chem. (2009) [Pubmed]
  8. Interleukin-18 regulates both Th1 and Th2 responses. Nakanishi, K., Yoshimoto, T., Tsutsui, H., Okamura, H. Annu. Rev. Immunol. (2001) [Pubmed]
  9. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Martinon, F., Tschopp, J. Cell (2004) [Pubmed]
  10. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Netea, M.G., Joosten, L.A., Lewis, E., Jensen, D.R., Voshol, P.J., Kullberg, B.J., Tack, C.J., van Krieken, H., Kim, S.H., Stalenhoef, A.F., van de Loo, F.A., Verschueren, I., Pulawa, L., Akira, S., Eckel, R.H., Dinarello, C.A., van den Berg, W., van der Meer, J.W. Nat. Med. (2006) [Pubmed]
  11. Recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) expressing mouse IL-18 augments Th1 immunity and macrophage cytotoxicity. Luo, Y., Yamada, H., Chen, X., Ryan, A.A., Evanoff, D.P., Triccas, J.A., O'Donnell, M.A. Clin. Exp. Immunol. (2004) [Pubmed]
  12. A critical role for interleukin 18 in primary and memory effector responses to Listeria monocytogenes that extends beyond its effects on Interferon gamma production. Neighbors, M., Xu, X., Barrat, F.J., Ruuls, S.R., Churakova, T., Debets, R., Bazan, J.F., Kastelein, R.A., Abrams, J.S., O'Garra, A. J. Exp. Med. (2001) [Pubmed]
  13. Intensification of antitumor effect by T helper 1-dominant adoptive immunogene therapy for advanced orthotopic colon cancer. Nakamori, M., Iwahashi, M., Nakamura, M., Ueda, K., Zhang, X., Yamaue, H. Clin. Cancer Res. (2003) [Pubmed]
  14. Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity. Ju, D.W., Yang, Y., Tao, Q., Song, W.G., He, L., Chen, G., Gu, S., Ting, C.C., Cao, X. Gene Ther. (2000) [Pubmed]
  15. Interleukin 18 contributes to host resistance and gamma interferon production in mice infected with virulent Salmonella typhimurium. Mastroeni, P., Clare, S., Khan, S., Harrison, J.A., Hormaeche, C.E., Okamura, H., Kurimoto, M., Dougan, G. Infect. Immun. (1999) [Pubmed]
  16. Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1beta are differentially regulated in human blood mononuclear cells and mouse spleen cells. Puren, A.J., Fantuzzi, G., Dinarello, C.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  17. Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice. Shimoda, K., Tsutsui, H., Aoki, K., Kato, K., Matsuda, T., Numata, A., Takase, K., Yamamoto, T., Nukina, H., Hoshino, T., Asano, Y., Gondo, H., Okamura, T., Okamura, S., Nakayama, K., Nakanishi, K., Niho, Y., Harada, M. Blood (2002) [Pubmed]
  18. Pro-Th1 cytokines promote Fas-dependent apoptosis of immature peripheral basophils. Schneider, E., Tonanny, M.B., Lisbonne, M., Leite-de-Moraes, M., Dy, M. J. Immunol. (2004) [Pubmed]
  19. IFN-gamma-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma. Wild, J.S., Sigounas, A., Sur, N., Siddiqui, M.S., Alam, R., Kurimoto, M., Sur, S. J. Immunol. (2000) [Pubmed]
  20. IL-18 induces monocyte chemotactic protein-1 production in macrophages through the phosphatidylinositol 3-kinase/Akt and MEK/ERK1/2 pathways. Yoo, J.K., Kwon, H., Khil, L.Y., Zhang, L., Jun, H.S., Yoon, J.W. J. Immunol. (2005) [Pubmed]
  21. Interleukin-18 (interferon-gamma-inducing factor) is produced by osteoblasts and acts via granulocyte/macrophage colony-stimulating factor and not via interferon-gamma to inhibit osteoclast formation. Udagawa, N., Horwood, N.J., Elliott, J., Mackay, A., Owens, J., Okamura, H., Kurimoto, M., Chambers, T.J., Martin, T.J., Gillespie, M.T. J. Exp. Med. (1997) [Pubmed]
  22. Pathophysiological roles of interleukin-18 in inflammatory liver diseases. Tsutsui, H., Matsui, K., Okamura, H., Nakanishi, K. Immunol. Rev. (2000) [Pubmed]
  23. Inhibition of early airway neutrophilia does not affect development of airway hyperresponsiveness. Taube, C., Nick, J.A., Siegmund, B., Duez, C., Takeda, K., Rha, Y.H., Park, J.W., Joetham, A., Poch, K., Dakhama, A., Dinarello, C.A., Gelfand, E.W. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  24. Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Elhage, R., Jawien, J., Rudling, M., Ljunggren, H.G., Takeda, K., Akira, S., Bayard, F., Hansson, G.K. Cardiovasc. Res. (2003) [Pubmed]
  25. Exacerbated and prolonged allergic and non-allergic inflammatory cutaneous reaction in mice with targeted interleukin-18 expression in the skin. Kawase, Y., Hoshino, T., Yokota, K., Kuzuhara, A., Kirii, Y., Nishiwaki, E., Maeda, Y., Takeda, J., Okamoto, M., Kato, S., Imaizumi, T., Aizawa, H., Yoshino, K. J. Invest. Dermatol. (2003) [Pubmed]
  26. Topical suplatast tosilate (IPD) ameliorates Th2 cytokine-mediated dermatitis in caspase-1 transgenic mice by downregulating interleukin-4 and interleukin-5. Murakami, T., Yamanaka, K., Tokime, K., Kurokawa, I., Tsutsui, H., Nakanishi, K., Mizutani, H. Br. J. Dermatol. (2006) [Pubmed]
  27. IL-18 binding and inhibition of interferon gamma induction by human poxvirus-encoded proteins. Xiang, Y., Moss, B. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  28. IFN-gamma up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages. Kim, Y.M., Im, J.Y., Han, S.H., Kang, H.S., Choi, I. J. Immunol. (2000) [Pubmed]
  29. Interleukin-18 induces activation and association of p56(lck) and MAPK in a murine TH1 clone. Tsuji-Takayama, K., Matsumoto, S., Koide, K., Takeuchi, M., Ikeda, M., Ohta, T., Kurimoto, M. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  30. IFN-gamma-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones. Tsutsui, H., Nakanishi, K., Matsui, K., Higashino, K., Okamura, H., Miyazawa, Y., Kaneda, K. J. Immunol. (1996) [Pubmed]
  31. Interleukin-18 plays a role in both the alum-induced T helper 2 response and the T helper 1 response induced by alum-adsorbed interleukin-12. Pollock, K.G., Conacher, M., Wei, X.Q., Alexander, J., Brewer, J.M. Immunology (2003) [Pubmed]
  32. Differential effect of IL-18 on endothelial cell apoptosis mediated by TNF-alpha and Fas (CD95). Mariño, E., Cardier, J.E. Cytokine (2003) [Pubmed]
  33. Interleukin-18 stimulates hematopoietic cytokine and growth factor formation and augments circulating granulocytes in mice. Ogura, T., Ueda, H., Hosohara, K., Tsuji, R., Nagata, Y., Kashiwamura, S., Okamura, H. Blood (2001) [Pubmed]
  34. Interleukin-18 suppresses adiponectin expression in 3T3-L1 adipocytes via a novel signal transduction pathway involving ERK1/2-dependent NFATc4 phosphorylation. Chandrasekar, B., Patel, D.N., Mummidi, S., Kim, J.W., Clark, R.A., Valente, A.J. J. Biol. Chem. (2008) [Pubmed]
  35. IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and promotes resolution of, bacterial infection in mice. Bohn, E., Sing, A., Zumbihl, R., Bielfeldt, C., Okamura, H., Kurimoto, M., Heesemann, J., Autenrieth, I.B. J. Immunol. (1998) [Pubmed]
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