Interleukin 18

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IL18 Solution Structure.rsh.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases IL18, IGIF, IL-18, IL-1g, IL1F4, interleukin 18
External IDs OMIM: 600953 MGI: 107936 HomoloGene: 1200 GeneCards: IL18
Gene location (Human)
Chromosome 11 (human)
Chr. Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for IL18
Genomic location for IL18
Band 11q23.1 Start 112,143,251 bp[1]
End 112,164,117 bp[1]
RNA expression pattern
PBB GE IL18 206295 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 11: 112.14 – 112.16 Mb Chr 11: 50.55 – 50.58 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Interleukin-18 (IL18, also known as interferon-gamma inducing factor) is a protein which in humans is encoded by the IL18 gene.[5][6] The protein encoded by this gene is a proinflammatory cytokine.


IL-18 is a cytokine that belongs to the IL-1 superfamily and is produced by macrophages and other cells. IL-18 works by binding to the interleukin-18 receptor, and together with IL-12 it induces cell-mediated immunity following infection with microbial products like lipopolysaccharide (LPS). After stimulation with IL-18, natural killer (NK) cells and certain T cells release another important cytokine called interferon-γ (IFN-γ) or type II interferon that plays an important role in activating the macrophages or other cells.

The combination of this cytokine and IL12 has been shown to inhibit IL-4 dependent IgE and IgG1 production, and enhance IgG2a production in B cells. IL-18 binding protein (IL18BP) can specifically interact with this cytokine, and thus negatively regulate its biological activity.[7]

Clinical significance[edit]

Apart from its physiological role, IL-18 is also able to induce severe inflammatory reactions, which suggests its role in certain inflammatory disorders.

Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein to interleukin 18 are significantly increased in adenomyosis patients in comparison to normal people, indicating a role in its pathogenesis.[8]

IL-18 has been implicated as an inflammatory mediator of Hashimoto's thyroiditis, the most common cause of autoimmune hypothyroidism. IL-18 is up regulated by interferon-gamma.[9]

IL-18 has also been found to increase the Alzheimer's disease-associated amyloid-beta production in human neuron cells.[10]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000150782 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039217 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K (November 1995). "Cloning of a new cytokine that induces IFN-gamma production by T cells". Nature. 378 (6552): 88–91. doi:10.1038/378088a0. PMID 7477296. 
  6. ^ Nolan KF, Greaves DR, Waldmann H (July 1998). "The human interleukin 18 gene IL18 maps to 11q22.2-q22.3, closely linked to the DRD2 gene locus and distinct from mapped IDDM loci". Genomics. 51 (1): 161–3. doi:10.1006/geno.1998.5336. PMID 9693051. 
  7. ^ "Entrez Gene: IL18 interleukin 18 (interferon-gamma-inducing factor)". 
  8. ^ Huang HY, Yu HT, Chan SH, Lee CL, Wang HS, Soong YK (June 2010). "Eutopic endometrial interleukin-18 system mRNA and protein expression at the level of endometrial-myometrial interface in adenomyosis patients". Fertil. Steril. 94 (1): 33–9. doi:10.1016/j.fertnstert.2009.01.132. PMID 19394601. 
  9. ^ Liu Z, Wang H, Xiao W, Wang C, Liu G, Hong T (October 2010). "Thyrocyte interleukin-18 expression is up-regulated by interferon-γ and may contribute to thyroid destruction in Hashimoto's thyroiditis". Int J Exp Pathol. 91 (5): 420–5. doi:10.1111/j.1365-2613.2010.00715.x. PMC 3003839Freely accessible. PMID 20586818. 
  10. ^ Sutinen EM, Pirttilä T, Anderson G, Salminen A, Ojala JO (2012). "Pro-inflammatory interleukin-18 increases Alzheimer's disease-associated amyloid-β production in human neuron-like cells". J Neuroinflammation. 9: 199. doi:10.1186/1742-2094-9-199. PMC 3458954Freely accessible. PMID 22898493. 

Further reading[edit]

  • Biet F, Locht C, Kremer L (2002). "Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens". J. Mol. Med. 80 (3): 147–62. doi:10.1007/s00109-001-0307-1. PMID 11894141. 
  • Nakanishi K (2002). "[Regulation of Th1 and Th2 immune responses by IL-18]". Kekkaku. 77 (2): 87–93. PMID 11905033. 
  • Reddy P, Ferrara JL (2003). "Role of interleukin-18 in acute graft-vs-host disease". J. Lab. Clin. Med. 141 (6): 365–71. doi:10.1016/S0022-2143(03)00028-3. PMID 12819633. 
  • Kanai T, Uraushihara K, Totsuka T, et al. (2003). "Macrophage-derived IL-18 targeting for the treatment of Crohn's disease". Current drug targets. Inflammation and allergy. 2 (2): 131–6. doi:10.2174/1568010033484250. PMID 14561165. 
  • Matsui K, Tsutsui H, Nakanishi K (2005). "Pathophysiological roles for IL-18 in inflammatory arthritis". Expert Opin. Ther. Targets. 7 (6): 701–24. doi:10.1517/14728222.7.6.701. PMID 14640907. 
  • Yoshimoto T, Nakanishi K (2006). "Roles of IL-18 in basophils and mast cells". Allergology International. 55 (2): 105–13. doi:10.2332/allergolint.55.105. PMID 17075246. 
  • Orozco A, Gemmell E, Bickel M, Seymour GJ (2007). "Interleukin 18 and periodontal disease". J. Dent. Res. 86 (7): 586–93. doi:10.1177/154405910708600702. PMID 17586702.