Interleukin 18

For the Soviet four-engined turboprop airliner dubbed "Il-18", see Ilyushin Il-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
Species	Human	Mouse
Entrez	3606	16173
Ensembl	ENSG00000150782	ENSMUSG00000039217
UniProt	Q14116	P70380
RefSeq (mRNA)	NM_001243211	NM_008360
RefSeq (protein)	NP_001230140	NP_032386
Location (UCSC)	Chr 11: 112.14 – 112.16 Mb	Chr 9: 50.58 – 50.58 Mb
PubMed search	[1]	[2]

Interleukin-18 (IL18, also known as interferon-gamma inducing factor) is a protein which in humans is encoded by the IL18 gene. 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.

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.

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.

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

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. 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.