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Gene Review

Il18  -  interleukin 18

Rattus norvegicus

Synonyms: IFN-gamma-inducing factor, IL-1 gamma, IL-18, Igif, Interferon gamma-inducing factor, ...
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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

  • Strong immunoreactivity for IL-18 was detected in the medial smooth muscle cells at days 2 and 7 after balloon injury and in proliferating/migrating smooth muscle cells in neointima at day 14 [1].
  • Increased expression of IL-18 and IL-18Ralpha/beta mRNA was detectable in carotid arteries from days 2 to 14 after angioplasty [1].
  • Rat brain IL-18 shows close homology to mouse and human IL-18, and to the recently published sequence from the rat adrenal gland [12].
  • Interleukin-18 (IL-18) is a pro-inflammatory cytokine predominantly studied as a modulator of immune functions and also produced in the adrenal cortex following activation of the hypothalamic-pituitary-adrenal axis [10].
  • This study is the first to demonstrate the detection of IL-18 in the thyroid gland [9].

Associations of Il18 with chemical compounds


Regulatory relationships of Il18


Other interactions of Il18

  • This regulation is potentially mediated by milk TGF-beta2, as well as endogenous IL-18 [18].
  • We assessed the role of TGF-beta in mediating mucosal immune development and specifically the effect on endogenous IL-18 [18].
  • With regard to IFN-gamma-inducing cytokines, we observed enhanced IL-12 mRNA levels in vivo, whereas IL-18 gene expression was slightly decreased [19].
  • In conclusion, we demonstrated for the first time that IL-18 is a prohypernociceptive cytokine that induces mechanical hypernociception mediated by endothelin, via ET(B) receptor [20].
  • Thus, the activated microglia-derived cytokines, TNF-alpha and IL-18, may either inhibit the neuronal differentiation or induce neuronal cell death in the NPC culture, whereas these cells may also produce factors to improve the neurite branching in the NPC culture [21].

Analytical, diagnostic and therapeutic context of Il18


  1. Neutralization of interleukin-18 inhibits neointimal formation in a rat model of vascular injury. Maffia, P., Grassia, G., Di Meglio, P., Carnuccio, R., Berrino, L., Garside, P., Ianaro, A., Ialenti, A. Circulation (2006) [Pubmed]
  2. Role of IL-18 in acute lung inflammation. Jordan, J.A., Guo, R.F., Yun, E.C., Sarma, V., Warner, R.L., Crouch, L.D., Senaldi, G., Ulich, T.R., Ward, P.A. J. Immunol. (2001) [Pubmed]
  3. The pro-atherogenic cytokine interleukin-18 induces CXCL16 expression in rat aortic smooth muscle cells via MyD88, interleukin-1 receptor-associated kinase, tumor necrosis factor receptor-associated factor 6, c-Src, phosphatidylinositol 3-kinase, Akt, c-Jun N-terminal kinase, and activator protein-1 signaling. Chandrasekar, B., Mummidi, S., Valente, A.J., Patel, D.N., Bailey, S.R., Freeman, G.L., Hatano, M., Tokuhisa, T., Jensen, L.E. J. Biol. Chem. (2005) [Pubmed]
  4. Neutralizing antibodies to IFN-gamma-inducing factor prevent experimental autoimmune encephalomyelitis. Wildbaum, G., Youssef, S., Grabie, N., Karin, N. J. Immunol. (1998) [Pubmed]
  5. Inhibition of angiogenesis by interleukin-4 gene therapy in rat adjuvant-induced arthritis. Haas, C.S., Amin, M.A., Allen, B.B., Ruth, J.H., Haines, G.K., Woods, J.M., Koch, A.E. Arthritis Rheum. (2006) [Pubmed]
  6. Tissue-specific expression of rat IL-18 gene and response to adrenocorticotropic hormone treatment. Sugama, S., Kim, Y., Baker, H., Tinti, C., Kim, H., Joh, T.H., Conti, B. J. Immunol. (2000) [Pubmed]
  7. C6 glioma cells retrovirally engineered to express IL-18 and Fas exert FasL-dependent cytotoxicity against glioma formation. Zhang, Y., Wang, C., Zhang, Y., Sun, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  8. Long-lasting gene expression by particle-mediated intramuscular transfection modified with bupivacaine: combinatorial gene therapy with IL-12 and IL-18 cDNA against rat sarcoma at a distant site. Ajiki, T., Murakami, T., Kobayashi, Y., Hakamata, Y., Wang, J., Inoue, S., Ohtsuki, M., Nakagawa, H., Kariya, Y., Hoshino, Y., Kobayashi, E. Cancer Gene Ther. (2003) [Pubmed]
  9. Thyroid-stimulating hormone induces interleukin-18 gene expression in FRTL-5 cells: immunohistochemical detection of interleukin-18 in autoimmune thyroid disease. Takiyama, Y., Miyokawa, N., Tokusashi, Y., Ito, K., Kato, S., Kimura, S., Sato, K., Katagiri, M. Thyroid (2002) [Pubmed]
  10. Neurons of the superior nucleus of the medial habenula and ependymal cells express IL-18 in rat CNS. Sugama, S., Cho, B.P., Baker, H., Joh, T.H., Lucero, J., Conti, B. Brain Res. (2002) [Pubmed]
  11. Interleukin-18 is expressed in rat testis and may promote germ cell growth. Strand, M.L., Wahlgren, A., Svechnikov, K., Zetterström, C., Setchell, B.P., Söder, O. Mol. Cell. Endocrinol. (2005) [Pubmed]
  12. Cloning of rat brain interleukin-18 cDNA. Culhane, A.C., Hall, M.D., Rothwell, N.J., Luheshi, G.N. Mol. Psychiatry (1998) [Pubmed]
  13. A novel role for IL-18 in corticosterone-mediated intestinal damage in a two-hit rodent model of alcohol intoxication and injury. Li, X., Rana, S.N., Schwacha, M.G., Chaudry, I.H., Choudhry, M.A. J. Leukoc. Biol. (2006) [Pubmed]
  14. Gene expression profiling identifies a unique androgen-mediated inflammatory/immune signature and a PTEN (phosphatase and tensin homolog deleted on chromosome 10)-mediated apoptotic response specific to the rat ventral prostate. Desai, K.V., Michalowska, A.M., Kondaiah, P., Ward, J.M., Shih, J.H., Green, J.E. Mol. Endocrinol. (2004) [Pubmed]
  15. The pro-inflammatory cytokine interleukin-18 impairs long-term potentiation and NMDA receptor-mediated transmission in the rat hippocampus in vitro. Curran, B., O'Connor, J.J. Neuroscience (2001) [Pubmed]
  16. TNF-alpha and H2O2 induce IL-18 and IL-18R beta expression in cardiomyocytes via NF-kappa B activation. Chandrasekar, B., Colston, J.T., de la Rosa, S.D., Rao, P.P., Freeman, G.L. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  17. Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor. Halpern, M.D., Dominguez, J.A., Dvorakova, K., Holubec, H., Williams, C.S., Meza, Y.G., Ruth, M.C., Dvorak, B. J. Pediatr. Gastroenterol. Nutr. (2003) [Pubmed]
  18. Maternal milk regulation of cell infiltration and interleukin 18 in the intestine of suckling rat pups. Penttila, I.A., Flesch, I.E., McCue, A.L., Powell, B.C., Zhou, F.H., Read, L.C., Zola, H. Gut (2003) [Pubmed]
  19. Experimental silicosis: a shift to a preferential IFN-gamma-based Th1 response in thoracic lymph nodes. Garn, H., Friedetzky, A., Kirchner, A., Jäger, R., Gemsa, D. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  20. Interleukin-18 induces mechanical hypernociception in rats via endothelin acting on ETB receptors in a morphine-sensitive manner. Verri, W.A., Schivo, I.R., Cunha, T.M., Liew, F.Y., Ferreira, S.H., Cunha, F.Q. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  21. Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture. Liu, Y.P., Lin, H.I., Tzeng, S.F. Brain Res. (2005) [Pubmed]
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