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IL18 Gene
IL18 Gene (Interleukin-18)
Introduction
Il18 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Pathway Diagram
Overview
The IL18 Gene encodes interleukin-18, a pro-inflammatory cytokine belonging to the IL-1 family. IL-18 plays a crucial role in innate immunity, inflammation, and has been strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, ALS, and multiple sclerosis. Originally discovered as an interferon-gamma (IFN-γ) inducing factor, IL-18 is now recognized as a key mediator of neuroinflammation in the central nervous system. [@dinarello2013]
IL18 Gene (Interleukin-18)
Introduction
Il18 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Pathway Diagram
Overview
The IL18 Gene encodes interleukin-18, a pro-inflammatory cytokine belonging to the IL-1 family. IL-18 plays a crucial role in innate immunity, inflammation, and has been strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, ALS, and multiple sclerosis. Originally discovered as an interferon-gamma (IFN-γ) inducing factor, IL-18 is now recognized as a key mediator of neuroinflammation in the central nervous system. [@dinarello2013]
<div class="infobox infobox-gene"> [@hafizi2020]
<table> [@ojala2009]
<tr><th colspan="2" style="background:#f0f0f0;">IL18 - Interleukin-18</th></tr> [@sugama2020]
<tr><td><b>Full Name</b></td><td>Interleukin-18</td></tr> [@debyser2021]
<tr><td><b>Chromosome</b></td><td>11q22.2-q22.3</td></tr> [@almer2002]
<tr><td><b>NCBI Gene ID</b></td><td>[3609](https://www.ncbi.nlm.nih.gov/gene/3609)</td></tr> [@zetterberg2021]
<tr><td><b>OMIM ID</b></td><td>[600953](https://www.omim.org/entry/600953)</td></tr> [@kaplanski2018]
<tr><td><b>Ensembl ID</b></td><td>ENSG00000150782</td></tr> [@mori2019]
<tr><td><b>UniProt ID</b></td><td>[Q14116](https://www.uniprot.org/uniprot/Q14116)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>Alzheimer's Disease, Parkinson's Disease, ALS, Multiple Sclerosis, Stroke, Traumatic Brain Injury, Rheumatoid Arthritis, Inflammatory Bowel Disease</td></tr>
</table>
</div>
Protein Structure
IL-18 is synthesized as a biologically inactive propeptide requiring proteolytic processing for activation:
Precursor Structure
- Pro-IL-18 (24 kDa): 192 amino acid precursor
- N-terminal propeptide: Removed by caspase-1 cleavage
- Mature IL-18 (18 kDa): 157 amino acid active cytokine
Structural Features
- β-trefoil fold: Characteristic of IL-1 cytokine family
- Signal peptide: Directs secretion via non-classical pathway
- No disulfide bonds: Unusual for secreted proteins
- Glycosylation sites: N-linked glycosylation affects stability
Molecular Function
Biosynthesis and Activation
IL-18 production and activation involves multiple steps:
Receptor Signaling
IL-18 signaling through its receptor complex:
Receptor Complex
- IL-18Rα (IL1RL1): Binding subunit, expressed on target cells
- IL-18Rβ (IL1RAP): Co-receptor, required for signaling
- IL-18BP: Natural antagonist, regulates IL-18 activity
Signaling Cascade
Brain Expression
Cellular Sources in CNS
IL-18 is produced by multiple cell types in the brain:
| Cell Type | Expression Level | Notes |
|-----------|------------------|-------|
| [Microglia](/entities/microglia) | High | Primary source in CNS; constitutive expression |
| [Astrocytes](/entities/astrocytes) | Moderate | Upregulated in disease states |
| [Neurons](/entities/neurons) | Low-Basal | Activity-dependent expression |
| Oligodendrocytes | Low | Limited data |
| [Pericytes](/cell-types/pericytes) | Moderate | Contributes to neurovascular inflammation |
Induction in Neurodegeneration
Various pathological stimuli trigger IL-18 production:
- Amyloid-beta (Aβ): Activates [NLRP3](/entities/nlrp3-inflammasome) inflammasome in [microglia](/cell-types/microglia-neuroinflammation)[@hafizi2020]
- [Alpha-synuclein](/proteins/alpha-synuclein): Activates microglia via TLR2/4
- [TDP-43](/proteins/tdp-43) aggregates: Triggers inflammasome activation
- Ischemia: Rapid IL-18 induction in stroke
Disease Associations
Alzheimer's Disease
IL-18 is a critical mediator in AD neuroinflammation:
- Elevated in AD Brain: IL-18 protein and mRNA increased in AD [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex)[@ojala2009]
- CSF Biomarker: IL-18 levels correlate with disease severity and progression
- Synaptic Dysfunction: IL-18 impairs [long-term potentiation](/mechanisms/long-term-potentiation) (LTP)
- Amyloid Pathology: Promotes [Aβ](/proteins/amyloid-beta) production and reduces clearance
- [Tau](/proteins/tau) Pathology: Enhances [tau](/proteins/tau) phosphorylation via GSK3β activation
- Genetic Variants: IL18 promoter polymorphisms associated with AD risk
Parkinson's Disease
IL-18 contributes to dopaminergic neuron degeneration:
- Elevated in PD Brain: Increased IL-18 in substantia nigra and striatum
- CSF Levels: Higher in PD patients vs controls, correlates with motor symptoms
- Dopaminergic Toxicity: IL-18/IFN-γ axis promotes neuron death[@sugama2020]
- Microglial Activation: Sustained neuroinflammation via NLRP3
- Therapeutic Target: IL-18 blocking strategies show promise in models
Amyotrophic Lateral Sclerosis (ALS)
IL-18 involvement in motor neuron disease:
- Elevated CSF Levels: IL-18 increased in sporadic and familial ALS
- Disease Progression: Correlates with rate of functional decline
- Motor Neuron Death: IL-18 synergizes with other cytokines
- Inflammasome Activation: [TDP-43](/mechanisms/tdp-43-proteinopathy) and SOD1 aggregates trigger NLRP3[@debyser2021]
- Therapeutic Implications: Targeting IL-18 may slow progression
Multiple Sclerosis
IL-18 in autoimmune demyelination:
- Active Lesions: High IL-18 in demyelinating plaques
- Th1/Th17 Response: Promotes IFN-γ and IL-17 production
- EAE Model: IL-18 critical for disease development
- Therapeutic Target: IL-18 blockade reduces disease severity
Stroke and Traumatic Brain Injury
- Ischemic Stroke: Rapid IL-18 induction in infarcted tissue
- Excitotoxicity: IL-18 amplifies glutamate-induced damage
- [Blood-Brain Barrier](/entities/blood-brain-barrier): IL-18 disrupts BBB integrity
- Prognostic Marker: IL-18 predicts functional outcome
Signaling Pathways
Inflammatory Cascade
Cross-talk Pathways
- NF-κB Pathway: Positive feedback for IL-18 production
- IFN-γ Axis: IL-18 induces IFN-γ, creating inflammatory loop
- JAK/STAT Signaling: IL-18 activates STAT1
- MAPK Pathways: ERK, JNK, p38 activation
Therapeutic Implications
Inhibition Strategies
Clinical Trials
- IL-18BP: Phase I/II trials in inflammatory diseases
- Caspase-1 inhibitors: Tested in autoimmune conditions
- Anti-IL-18 strategies: Being explored in neurodegeneration
Biomarker Potential
IL-18 as biomarker in neurodegeneration:
- Diagnostic: Differentiates disease from controls
- Prognostic: Predicts disease progression
- Therapeutic: Monitors treatment response
Key Publications
Background
The study of Il18 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
- [Inflammation Pathway](/mechanisms/neuroinflammation)
- [NLRP3 Inflammasome](/mechanisms/nlrp3-inflammasome) Caspase-1
- Pyroptosis Pathway
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [ALS](/diseases/amyotrophic-lateral-sclerosis)
- [Multiple Sclerosis](/diseases/multiple-sclerosis)
- [Stroke](/diseases/stroke)
- Interleukin-1 Beta
- Interferon-Gamma
External Links
- [NCBI Gene: IL18](https://www.ncbi.nlm.nih.gov/gene/3609)
- [UniProt: Q14116](https://www.uniprot.org/uniprot/Q14116)
- [Ensembl: ENSG00000150782](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000150782)
- [GeneCards: IL18](https://www.genecards.org/cgi-bin/carddisp.pl?gene=IL18)
- [Human Protein Atlas](https://www.proteinatlas.org/ENSG00000150782-IL18)
References
Pathway Diagram
The following diagram shows the key molecular relationships involving IL18 Gene discovered through SciDEX knowledge graph analysis:
▸Metadataorigin_type: v1_polymorphic_backfill
| slug | genes-il18 |
| kg_node_id | IL18 |
| entity_type | gene |
| origin_type | v1_polymorphic_backfill |
| source_table | wiki_pages |
| wiki_page_id | wp-bc297209d964 |
| __merged_from | {'merged_at': '2026-05-13', 'unprefixed_id': 'genes-il18'} |
| _schema_version | 1 |
No provenance edges found
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