gene

IL6

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about IL6: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

2138Connections

0Hypotheses

2Analyses

50Outgoing

50Incoming

0Experiments

2Debates

Summary

Interleukin-6 (IL-6) is a pleiotropic cytokine that functions as both a pro-inflammatory mediator and an immunomodulatory molecule in the central nervous system. In neurodegeneration, IL-6 is produced by microglia, astrocytes, and neurons in response to pathological stimuli, and its dysregulation contributes to neuroinflammatory cascades implicated in Alzheimer's disease pathogenesis. The IL-6/STAT3 signaling pathway interacts with multiple AD-relevant mechanisms, including the cGAS-STING innate immune pathway that drives type I interferon responses. IL-6 deficiency in mouse models reduces neuroinflammation and improves cognitive outcomes, demonstrating its disease-promoting role. Elevated IL-6 levels are observed in AD brain tissue and cerebrospinal fluid, and genetic variants in IL-6 have been associated with AD risk. Therapeutic approaches targeting IL-6 or its receptor (IL-6R) are under investigation for neurodegenerative diseases, though systemic immunosuppression risks must be carefully managed. The dual role of IL-6 in both inflammatory responses and normal brain function makes targeting this cytokine particularly challenging.

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🧬 Gene Info

Gene Symbol	IL6
Full Name	Interleukin 6
Function	is an important component in the neurobiology of neurodegenerative diseases.
Pathways	Akt, Amyloid, Apoptosis, Autophagy, Epigenetic
Ensembl ID	ENSG00000136244
GeneCards	IL6
Human Protein Atlas	IL6
IL-6R (CD126)	Membrane-bound receptor
gp130 (CD130)	Signal-transducing subunit (shared with other IL-6 family cytokines)
JAK/STAT3	Primary signaling pathway
MAPK/ERK	Secondary signaling cascade
Soluble IL-6R (sIL-6R)	Generated by proteolytic cleavage or alternative splicing
Trans-signaling	Enables IL-6 response in cells lacking membrane IL-6R
Pro-inflammatory	Trans-signaling is primarily pro-inflammatory
Macrophages/Monocytes	Primary source, TLR-stimulated
Associated Diseases	AD, Aging, Als, Alzheimer, Alzheimer's disease
Known Drugs/Compounds	Andrographis paniculata, Anti-IL6 Antibody, DUPILUMAB, IRN, MELATONIN, quercetin
Interactions	A2M, ABCB1, ABCG2, ACACA, ACE, ACSL4
KG Connections	2137 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (4)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

flowchart TD
    IL6(["IL6"])
    INFLAMMATION("INFLAMMATION")
    Als["Als"]
    Inflammation["Inflammation"]
    Cancer["Cancer"]
    CANCER(["CANCER"])
    GENES(["GENES"])
    IL_6(["IL-6"])
    TNF(["TNF"])
    AKT1(["AKT1"])
    Tumor["Tumor"]
    Infection["Infection"]
    T_Cell_Differentiation("T Cell Differentiation")

    IL6 -->|"activates"| INFLAMMATION
    IL6 -->|"therapeutic target"| Als
    IL6 -.->|"inhibits"| Inflammation
    IL6 -->|"activates"| Cancer
    IL6 -->|"activates"| Inflammation
    IL6 -->|"activates"| CANCER
    IL6 -->|"therapeutic target"| GENES
    IL6 -->|"activates"| IL_6
    TNF -->|"activates"| IL6
    TNF -->|"therapeutic target"| IL6
    AKT1 -->|"therapeutic target"| IL6
    IL6 -->|"activates"| Als
    IL6 -->|"associated with"| Tumor
    IL6 -->|"activates"| Infection
    IL6 -->|"regulates"| T_Cell_Differentiation

    style IL6 fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (1329)

Target	Relation	Type	Str
Inflammation	activates	disease	1.00
CANCER	activates	gene	1.00
Als	therapeutic_target	disease	1.00
Cancer	activates	disease	1.00
INFLAMMATION	activates	phenotype	1.00
Inflammation	inhibits	disease	1.00
GENES	therapeutic_target	gene	1.00
IL-6	activates	gene	1.00
Frailty	biomarker_for	phenotype	0.95
Tumor	associated_with	disease	0.95
Th17 Cell	activates	cell_type	0.95
T Cell Differentiation	regulates	process	0.95
Infection	activates	disease	0.95
Als	activates	disease	0.95
oxidative stress response	participates_in	pathway	0.90
NEUROMYELITIS OPTICA SPECTRUM DISORDER	therapeutic_target	entity	0.90
Parkinson's Disease	promotes	disease	0.90
Mesolimbic Dopamine	downregulates	process	0.90
Apathy	mediates	phenotype	0.90
STAT3	activates	protein	0.90
Neuroinflammation	mediates	process	0.90
normal pituitary cell proliferation	inhibits	phenotype	0.90
Endotoxemia	associated_with	disease	0.90
STAT3	interacts_with	protein	0.90
JAK/STAT3 pathway	activates	pathway	0.90
pituitary tumor cell growth	activates	phenotype	0.90
ST6GAL1	contributes_to	gene	0.90
JAK1	activates	protein	0.90
ziltivekimab	targets	drug	0.90
atherosclerotic cardiovascular disease	associated_with	disease	0.90
GP130-STAT3 pathway	activates	pathway	0.90
Neurodegeneration	associated_with	process	0.90
JAK	activates	protein	0.87
Carcinoma	associated_with	disease	0.85
Vascular Dysfunction	promotes	phenotype	0.85
Neuromyelitis Optica Spectrum Disorder	contributes_to	disease	0.85
Frailty	biomarker_for	phenotype	0.85
Inflammation	associated_with	disease	0.85
Chronic Obstructive Pulmonary Disease	associated_with	disease	0.85
Atherosclerosis	therapeutic_target	disease	0.85
neuroinflammation	activates	phenotype	0.85
Cancer	inhibits	disease	0.85
Parkinson'S Disease	associated_with	disease	0.85
Tumor	therapeutic_target	disease	0.85
Recurrent Stroke	biomarker_for	disease	0.85
Tumor	inhibits	disease	0.85
kidney inflammation	mediates	process	0.85
Cancer	associated_with	disease	0.85
Tumor	activates	disease	0.85
Als	associated_with	disease	0.85

Incoming (809)

Source	Relation	Type	Str
AKT1	targets	gene	1.00
TNF	activates	gene	1.00
TNF	therapeutic_target	gene	1.00
IPA	downregulates	compound	0.95
Anti-IL6 Antibody	targets	drug	0.95
Lapiferin	downregulates	compound	0.92
Gallic Acid	downregulates	compound	0.90
Hearing Loss	upregulates	phenotype	0.90
high glucose	upregulates	compound	0.90
NRF2	regulates	gene	0.90
Ric	downregulates	process	0.90
h-6f1e8d32	targets	hypothesis	0.90
microglia	upregulates	cell_type	0.90
DTG	upregulates	entity	0.90
Microglia	upregulates	cell_type	0.90
Itaconate	downregulates	compound	0.90
ASTROCYTES	activates	cell_type	0.90
rutin	inhibits	drug	0.90
NFKB1	activates	gene	0.90
Urolithin A	inhibits	drug	0.90
Betulinic Acid	downregulates	compound	0.90
Pulmonary Vascular Endothelial Cell Senescence	upregulates	process	0.90
NF-kB	regulates	pathway	0.90
STAT3	activates	gene	0.90
Microglia	expressed_in	cell_type	0.88
NF-κB Signaling	upregulates	pathway	0.88
Dolutegravir	upregulates	drug	0.87
GPR37	upregulates	gene	0.85
Glucose	upregulates	compound	0.85
Brainstem-To-Basal Ganglia Circuit	involved_in	mechanism	0.85
STAT3	phosphorylates	entity	0.85
Ponicidin	downregulates	compound	0.85
Influenza A Virus	upregulates	disease	0.85
IL17	upregulates	pathway	0.85
Palmitoleic Acid	downregulates	compound	0.85
Vinpocetine	downregulates	drug	0.85
SOCS3	inhibits	protein	0.85
KCNK2	downregulates	gene	0.85
Rotenone	upregulates	compound	0.85
ER STRESS	mediates	entity	0.85
Leucocyanidin	downregulates	compound	0.85
Cachexia	upregulates	disease	0.85
PI3K-Akt signaling pathway	regulates	pathway	0.85
HEARING_LOSS	upregulates	phenotype	0.80
Andrographis paniculata	inhibits	drug	0.80
GNAI3	inhibits	gene	0.80
IL35	regulates	protein	0.80
NFKB	upregulates	gene	0.80
GNAI1	inhibits	gene	0.80
PSAP	mediates	protein	0.80

Targeting Hypotheses (0)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
No targeting hypotheses

Mentioning Analyses (2)

Scientific analyses that reference this entity

Why do systemic anti-inflammatory drugs fail in AD despite cardiovascular effica

clinical neurology | 2026-04-08 | 0 hypotheses

Which cell types show the most significant expression changes for neurodegenerat

neurodegeneration | 2026-04-03 | 7 hypotheses Top: 0.682

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (0)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
No papers found

Debates (2)

Multi-agent debates referencing this entity

The debate noted clinical failures of TNF-α and IL-6 inhibitors in AD despite th

closed · Rounds: 4 · Score: 0.79 · 2026-04-09

The debate mentioned gene expression profiling but did not specify which neural

closed · Rounds: 4 · Score: 0.93 · 2026-04-03

Related Research

Hypotheses and analyses mentioning IL6 in their description or question text

No additional research found

IL6