WordNet

any of several lymphokines that promote macrophages and killer T cells and B cells and other components of the immune system

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/07 13:42:21」(JST)

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Interleukin-18 (IL18, also known as interferon-gamma inducing factor) is a protein which in humans is encoded by the IL18 gene.^[1]^[2] The protein encoded by this gene is a proinflammatory cytokine.

Function

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.^[3]

Clinical significance

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.^[4]

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.^[5]

IL-18 has also been found to increase the Alzheimer's disease-associated amyloid-beta production in human neuron cells.^[6]

Age-related macular degeneration (AMD)

IL-18 acts as a guardian of eyesight by eliminating VEGF from the eye, thereby suppressing the production of damaging blood vessels behind the retina at the back of the eye. In pre-clinical models, IL-18 was administered intravenously, improving on the regular ocular injections of VEGF antibodies that is the standard of care.^[7] AMD is one of the most common forms of blindness among the aging. The two forms of AMD are 'dry' (the majority of cases) and wet, which causes 90% of blindings. Wet AMD causes sub-retinal blood vessels to grow excessively, which causes almost immediate central blindness. Prior treatment options for wet AMD were limited to the condition's end stages.^[7]

References

^ 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.
^ 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.
^ "Entrez Gene: IL18 interleukin 18 (interferon-gamma-inducing factor)".
^ 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.
^ 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 3003839. PMID 20586818.
^ 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 3458954. PMID 22898493.
^ ^a ^b Doyle SL, Ozaki E, Brennan K, Humphries MM, Mulfaul K, Keaney J, Kenna PF, Maminishkis A, Kiang AS, Saunders SP, Hams E, Lavelle EC, Gardiner C, Fallon PG, Adamson P, Humphries P, Campbell M (2014). "IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration". Sci Transl Med 6 (230): 230ra44. doi:10.1126/scitranslmed.3007616. PMID 24695684. Lay summary – Medicalxpress.com.

UpToDate Contents

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English Journal

Urocortin 2 protects heart and kidney structure and function in an ovine model of acute decompensated heart failure: Comparison with dobutamine.

Rademaker MT1, Ellmers LJ2, Charles CJ2, Mark Richards A2.
International journal of cardiology.Int J Cardiol.2015 Oct 15;197:56-65. doi: 10.1016/j.ijcard.2015.06.011. Epub 2015 Jun 15.
BACKGROUND: Renal dysfunction is a frequent complication and crucial determinant of outcome in acute decompensated heart failure (ADHF). The aim of the study was to assess urocortin 2 (Ucn2) as a short-term therapy in ADHF with a focus on its renal effects. Comparison was made with dobutamine to dis
PMID 26113475

Spot urine albumin to creatinine ratio outperforms novel acute kidney injury biomarkers in patients with acute myocardial infarction.

Tziakas D1, Chalikias G2, Kareli D2, Tsigalou C3, Risgits A2, Kikas P2, Makrygiannis D4, Chatzikyriakou S5, Kampouromiti G3, Symeonidis D4, Voudris V5, Konstantinides S2.
International journal of cardiology.Int J Cardiol.2015 Oct 15;197:48-55. doi: 10.1016/j.ijcard.2015.06.019. Epub 2015 Jun 18.
BACKGROUND: Acute kidney injury (AKI) is a frequent complication in patients hospitalized for acute myocardial infarction (AMI), and is associated with in-hospital and long-term morbidity and mortality. We prospectively assessed the diagnostic performance of spot urine albumin to creatinine ratio (u
PMID 26113474

The inflammasome and danger molecule signaling: at the crossroads of inflammation and pathogen persistence in the oral cavity.

Yilmaz Ö, Lee KL.
Periodontology 2000.Periodontol 2000.2015 Oct;69(1):83-95. doi: 10.1111/prd.12084.
Inflammasomes are an oligomeric assembly of multiprotein complexes that activate the caspase-1-dependent maturation and the subsequent secretion of inflammatory interleukin-1beta and interleukin-18 cytokines in response to a 'danger signal' in vertebrates. The assessment of their significance contin
PMID 26252403

Japanese Journal

Modulation of systemic and mucosal immunity against an inactivated vaccine of Newcastle disease virus by oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 and interferon-α

RAHMAN Md. Masudur,UYANGAA Erdenebelig,HAN Young Woo [他]
The journal of veterinary medical science 77(4), 395-403, 2015-04
NAID 40020462962

Modulation of systemic and mucosal immunity against an inactivated vaccine of Newcastle disease virus by oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 and interferon-α

, , , , , , ,
Journal of Veterinary Medical Science 77(4), 395-403, 2015
… Here, we investigated the systemic and mucosal immunomodulatory properties of oral co-administration of chicken interleukin-18 (chIL-18) and chicken interferon-α (chIFN-α) using attenuated Salmonella enterica serovar Typhimurium on an inactivated ND vaccine. …
NAID 130005067029

TGF-β Decreases the Stability of IL-18-Induced IFN-γ mRNA through the Expression of TGF-β-Induced Tristetraprolin in KG-1 Cells

, , [他],
Biological and Pharmaceutical Bulletin 38(4), 536-544, 2015
… We have previously reported that transforming growth factor-β (TGF-β) down-regulates interferon-γ (IFN-γ) production in an interleukin-18 (IL-18) treated mouse natural killer (NK) cell line, LNK5E6. … In LNK5E6 cells, TGF-β exhibited no inhibition of the IL-18-induced transcription of IFN-γ, but did stimulate the degradation of IFN-γ mRNA induced by IL-18. …
NAID 130005062261

Related Pictures

Interleukin 18 - Wikipedia Interleukin-18; Interferon-gamma-Inducing Factor; IFN-gamma-Inducing Factor; IL-18 Cellular targets of interleukin-18 in rheumatoid arthritis -- Dai et al. 66 (11): 1411 Interleukin-18-receptorer Frontiers | Interleukin-18 and IL-18 Binding Protein | Immunology Interleukin-22 Induces Interleukin-18 Expression from Epithelial Cells during Interleukin-18; Interferon-gamma-Inducing Factor; IFN-gamma-Inducing Factor; IL-18 Interleukin 18: a pleiotropic participant in chronic inflammation: Immunology Today

★リンクテーブル★

リンク元	「インターロイキン18」「IL-18」「インターロイキン-18」
拡張検索	「interleukin-18 receptor」「interleukin-18 receptor alpha subunit」「interleukin-18 receptor beta subunit」
関連記事	「interleukin」「interleukins」

「インターロイキン18」

Interleukin 18
	Solution structure of human IL-18
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1J0S, 2VXT, 3F62, 3WO2, 3WO3, 3WO4, 4EEE, 4EKX, 4HJJ, 4R6U
Identifiers
Symbols	IL18 ; IGIF; IL-18; IL-1g; IL1F4
External IDs	OMIM: 600953 MGI: 107936 HomoloGene: 1200 ChEMBL: 1741305 GeneCards: IL18 Gene
Gene ontology
Molecular function	• cytokine activity; • protein binding;
Cellular component	• extracellular region; • extracellular space; • cytosol; • extracellular exosome;
Biological process	• MAPK cascade; • angiogenesis; • inflammatory response; • immune response; • cell-cell signaling; • positive regulation of gene expression; • natural killer cell activation; • regulation of cell adhesion; • sleep; • lipopolysaccharide-mediated signaling pathway; • positive regulation of granulocyte macrophage colony-stimulating factor production; • positive regulation of interferon-gamma production; • positive regulation of interleukin-17 production; • positive regulation of natural killer cell proliferation; • positive regulation of tissue remodeling; • chemokine biosynthetic process; • T-helper 1 type immune response; • type 2 immune response; • interleukin-2 biosynthetic process; • interferon-gamma biosynthetic process; • positive regulation of activated T cell proliferation; • interleukin-13 biosynthetic process; • granulocyte macrophage colony-stimulating factor biosynthetic process; • positive regulation of NF-kappaB import into nucleus; • positive regulation of tyrosine phosphorylation of Stat3 protein; • negative regulation of myoblast differentiation; • positive regulation of inflammatory response; • positive regulation of NK T cell proliferation; • cellular response to lipopolysaccharide; • cellular response to organic cyclic compound;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;