IL11 Gene

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IL11 Gene

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IL11 (Interleukin-11)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">IL11 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>IL11</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[3609](https://www.ncbi.nlm.nih.gov/gene/3609)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>19q13.4</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>IL-6 family cytokine</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~19 kDa</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[P20815](https://www.uniprot.org/uniprot/P20815)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[147681](https://www.omim.org/entry/147681)</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>AGIF, OPN, oprelvekin</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">[Astrocytes](/cell-types/astrocytes)</td>
<td>Moderate-High</td>
</tr>
<tr>
<td class="label">[Neurons](/cell-types/neurons)</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Osteoblasts</td>
<td>High</td>
</tr>
<tr>
<td class="label">Fibroblasts</td>
<td>High</td>
</tr>
<tr>
<td class="label">Megakaryocytes</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cardiac fibroblasts</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cancer-associated fibroblasts</td>
<td>High</td>
</tr>
<tr>
<td class="label">As

...

IL11 (Interleukin-11)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">IL11 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>IL11</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[3609](https://www.ncbi.nlm.nih.gov/gene/3609)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>19q13.4</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>IL-6 family cytokine</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~19 kDa</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>[P20815](https://www.uniprot.org/uniprot/P20815)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[147681](https://www.omim.org/entry/147681)</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>AGIF, OPN, oprelvekin</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">[Astrocytes](/cell-types/astrocytes)</td>
<td>Moderate-High</td>
</tr>
<tr>
<td class="label">[Neurons](/cell-types/neurons)</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Osteoblasts</td>
<td>High</td>
</tr>
<tr>
<td class="label">Fibroblasts</td>
<td>High</td>
</tr>
<tr>
<td class="label">Megakaryocytes</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cardiac fibroblasts</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cancer-associated fibroblasts</td>
<td>High</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/lung-cancer" style="color:#ef9a9a">Lung Cancer</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">24 edges</a></td>
</tr>
</table>

Overview

Mermaid diagram (expand to render)

IL11 (Interleukin-11) is a member of the IL-6 family of cytokines that plays important roles in hematopoiesis, immune regulation, and tissue protection. Originally discovered for its role in platelet production, IL-11 has since been recognized for its anti-inflammatory properties and potential neuroprotective effects. In the nervous system, IL-11 is expressed in various cell types and has been implicated in neuroinflammation, astrocyte function, and neurodegenerative diseases["@du2016"][@gadient1998][@schwab2021].

Gene Overview

Structure

IL-11 is a secreted cytokine composed of 199 amino acids in its mature form. The protein adopts a characteristic four-helix bundle fold shared by the IL-6 family cytokines. The structure consists of:

Four α-helices (A, B, C, D) arranged in an up-up-down-down topology
Long connecting loops between helices
N-terminal signal peptide (21 amino acids) for secretion

The receptor-binding sites are located on the exposed surfaces of helices A and C, allowing interaction with the IL-11 receptor complex[@taga1992][@boehm1997].

Function

IL-11 has diverse biological functions spanning multiple organ systems:

Hematopoietic System

Thrombopoiesis: Stimulates platelet production from megakaryocytes, the primary clinical use of recombinant IL-11 (oprelvekin)[@metcalf2000]
Erythropoiesis: Supports red blood cell production
Megakaryocyte maturation: Promotes differentiation and platelet release

Immune System

Anti-inflammatory: Inhibits pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6)
T cell regulation: Modulates T cell responses and Th17 differentiation
Dendritic cell function: Affects antigen presentation and immune activation

Nervous System

Astrocyte function: Supports astrocyte survival, proliferation, and function[@kelley2020]
Neuroprotection: Exhibits protective effects in neuronal injury models[@vanelson2017]
Blood-brain barrier: May modulate BBB integrity and function
Neuroinflammation: Regulates glial activation and inflammatory responses[@schwab2021]

Other Tissues

Cardiac fibroblasts: Promotes cardiac fibroblast function and cardiac remodeling[@potla2012]
Cancer-associated fibroblasts: Supports tumor stroma in certain cancers[@ng2019]
Fibrosis: Plays roles in tissue fibrosis and wound healing[@steed2018]

Receptor Complex

IL-11 signals through a heterodimeric receptor complex:

IL11RA (Interleukin-11 Receptor Subunit Alpha, gene ID 3590): Ligand-binding subunit, primarily expressed in many cell types including neurons and astrocytes
IL6ST (GP130, gene ID 3572): Signal-transducing subunit, shared across the IL-6 family (IL-6, LIF, OSM, CNTF, CT-1)

The receptor complex forms a high-affinity binding site for IL-11, triggering intracellular signaling cascades.

Signaling Pathways

IL-11 activates multiple signaling cascades through GP130-mediated activation:

JAK/STAT pathway: Primarily JAK1/JAK2 and STAT3, the dominant pathway

STAT3 phosphorylation and dimerization
Nuclear translocation and gene transcription
Anti-apoptotic and anti-inflammatory gene expression

MAPK/ERK pathway: Cell proliferation and differentiation

RAS/RAF/MEK/ERK cascade activation
Cell growth and survival signals

PI3K/Akt pathway: Cell survival and metabolism

Akt activation promotes cell survival
Anti-apoptotic signaling

PKC pathway: Additional cellular responses

PKC isoform activation
Cytoskeletal and functional responses

Expression Pattern

IL-11 is widely expressed in various tissues with cell-type specificity:

Disease Associations

Neurodegenerative Diseases

Alzheimer's Disease

IL-11 has been studied in Alzheimer's disease pathogenesis. Chen et al. (2014) demonstrated altered IL-11 expression in AD brain tissue, with potential neuroprotective roles through anti-inflammatory mechanisms[@chen2014]. Further studies have shown:

IL-11 levels are reduced in AD patient brains
The cytokine exhibits protective effects against amyloid-beta toxicity[@zhang2019]
May modulate neuroinflammation characteristic of AD pathology

Parkinson's Disease

Astrocytic IL-11 has been investigated in PD models:

Astrocyte-derived IL-11 may provide neuroprotective effects in dopaminergic neurons[@kelley2020]
Anti-inflammatory properties may reduce microglial activation
Potential therapeutic target for slowing disease progression

Amyotrophic Lateral Sclerosis

Recent research has explored IL-11 in ALS:

Altered expression in ALS models and patient tissue
Cytokine therapy approaches using IL-11 have been investigated[@pooler2021]
May modulate neuroinflammation in motor neuron disease

Multiple Sclerosis

IL-11 has immunomodulatory roles in CNS autoimmunity:

Dysregulated expression in MS lesions
Potential therapeutic applications[@karlson2008]
Effects on T cell polarization and demyelination

Spinal Cord Injury

IL-11 demonstrates neuroprotective properties in injury models:

Promotes neuronal survival after injury[@vanelson2017]
Modulates inflammatory responses
Supports tissue repair mechanisms

Other Conditions

Thrombocytopenia: Recombinant human IL-11 (oprelvekin) FDA-approved for chemotherapy-induced thrombocytopenia
Inflammatory bowel disease: Immunomodulatory roles
Rheumatoid arthritis: Anti-inflammatory properties
Fibrosis: Both pro-fibrotic and anti-fibrotic roles depending on context[@steed2018]
Cancer: Controversial roles - both tumor-promoting and tumor-suppressing

IL-11 in Specific Disease Contexts

Alzheimer's Disease Pathogenesis

The involvement of IL-11 in Alzheimer's disease has been increasingly recognized through multiple lines of evidence. In AD brain tissue, IL-11 expression is altered compared to age-matched controls, with reduced levels observed in key brain regions affected by the disease[@chen2014]. This reduction may have pathophysiological consequences:

Amyloid-Beta Interaction:

IL-11 demonstrates protective effects against amyloid-beta toxicity in neuronal cultures
The cytokine can modulate the inflammatory response triggered by amyloid-beta accumulation
STAT3 activation by IL-11 may promote expression of anti-apoptotic proteins that protect neurons from amyloid-induced cell death

Neuroinflammatory Modulation:

IL-11 inhibits production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6
This anti-inflammatory effect may counteract the chronic neuroinflammation characteristic of AD
Astrocyte-derived IL-11 may provide a regulatory signal that limits microglial activation

Tau Pathology:

Evidence suggests IL-11 may influence tau phosphorylation pathways
The cytokine's effects on neuronal survival could impact tau-induced neurodegeneration
Further research is needed to fully delineate these mechanisms

Parkinson's Disease

In Parkinson's disease, IL-11 has emerged as a potentially protective cytokine in the context of dopaminergic neuron survival[@kelley2020]:

Astrocyte-Mediated Neuroprotection:

Astrocytes produce IL-11 in response to various cellular stresses
This astrocyte-derived IL-11 may protect neighboring dopaminergic neurons
The JAK/STAT pathway activated by IL-11 promotes expression of genes that support neuronal survival

Inflammatory Regulation:

IL-11's anti-inflammatory properties may reduce microglial activation in the substantia nigra
This could slow the progression of dopaminergic neuron loss
The cytokine may also modulate the inflammatory environment associated with alpha-synuclein pathology

Therapeutic Potential:

Recombinant IL-11 or IL-11 receptor agonists are being explored as disease-modifying approaches
Gene therapy strategies to increase IL-11 expression in the brain are under investigation
Combination approaches targeting multiple neuroprotective pathways may prove most effective

Amyotrophic Lateral Sclerosis

Recent studies have investigated IL-11 in ALS, where it may play complex roles[@pooler2021]:

Expression Changes:

Altered IL-11 expression has been observed in ALS patient tissue and animal models
Both increased and decreased IL-11 levels have been reported, depending on disease stage and model system
The cell type-specific sources of IL-11 in ALS remain under investigation

Potential Mechanisms:

IL-11 may modulate neuroinflammation in the motor neuron microenvironment
The cytokine's effects on RNA metabolism may intersect with other ALS-related pathways
STAT3-mediated signaling could promote motor neuron survival

Therapeutic Applications:

IL-11 cytokine therapy approaches are being explored in preclinical models
Delivery methods including viral vectors and protein administration are under investigation
Combination with other neuroprotective factors represents a promising direction

Multiple Sclerosis

In multiple sclerosis and related autoimmune demyelinating diseases, IL-11 has immunomodulatory properties that may be therapeutically relevant[@karlson2008]:

Immune System Effects:

IL-11 inhibits production of pro-inflammatory cytokines from immune cells
The cytokine promotes a shift toward anti-inflammatory immune responses
Regulatory T cell function may be enhanced by IL-11

CNS Effects:

In demyelinating lesions, IL-11 expression is dysregulated
The cytokine may support remyelination processes
Neuroprotective effects could limit axon loss during inflammatory attacks

Therapeutic Considerations:

Recombinant IL-11 has been investigated in clinical trials for MS
The complex immunomodulatory effects require careful dosing considerations
Patient selection based on cytokine profiles may improve outcomes

Spinal Cord Injury

IL-11 demonstrates neuroprotective properties in models of spinal cord injury[@vanelson2017]:

Acute Phase Effects:

IL-11 is upregulated following spinal cord injury
The cytokine promotes survival of damaged neurons
Anti-inflammatory effects limit secondary damage from inflammation

Recovery Promotion:

IL-11 supports tissue repair mechanisms
The cytokine may promote axonal regeneration
Functional recovery has been observed in animal models with IL-11 treatment

Mechanisms:

STAT3 activation is a key mediator of IL-11's protective effects
The cytokine modulates the injury microenvironment
Anti-apoptotic signaling contributes to neuronal survival

Signaling Pathway Details

JAK/STAT Pathway

The JAK/STAT pathway is the primary signaling cascade activated by IL-11 receptor engagement[@taga1992][@boehm1997]:

Receptor Activation:

IL-11 binding to IL11RA triggers association with IL6ST/GP130
GP130 dimerization brings JAK1 and JAK2 kinases into proximity
These JAKs transphosphorylate and become activated

STAT3 Activation:

Activated JAKs phosphorylate STAT3 on specific tyrosine residues
Phosphorylated STAT3 dimerizes and translocates to the nucleus
STAT3 dimers bind to specific DNA sequences and regulate gene transcription

Biological Effects:

Anti-apoptotic genes (Bcl-xL, Mcl-1, Survivin)
Anti-inflammatory genes (SOCS3, IL-10)
Acute phase proteins and tissue repair factors

MAPK/ERK Pathway

IL-11 also activates the MAPK cascade:

Ras/Raf/MEK/ERK Pathway:

GP130 engages adaptor proteins that activate Ras
Ras activates Raf kinase, which phosphorylates MEK
MEK phosphorylates ERK, which enters the nucleus

Cellular Outcomes:

Cell proliferation and differentiation
Cell survival signals
Integration with other pathways

PI3K/Akt Pathway

The PI3K/Akt pathway provides additional survival signals:

Signaling Cascade:

Receptor engagement activates PI3K
PI3K generates PIP3, which activates Akt
Akt phosphorylates multiple downstream targets

Neuroprotective Effects:

Phosphorylation of BAD, promoting cell survival
Activation of mTOR for protein synthesis
Regulation of glucose metabolism

Clinical Considerations

Pharmacokinetics

Recombinant human IL-11 (oprelvekin) has known pharmacokinetic properties:

Absorption: Subcutaneous administration results in slow absorption
Distribution: Limited tissue distribution, primarily circulating
Metabolism: Renal metabolism and clearance
Half-life: Approximately 6-7 hours in healthy subjects

Adverse Effects

Clinical use of IL-11 is associated with several side effects:

Fluid retention: Peripheral edema, weight gain
Fatigue: Common with systemically administered IL-11
Arthralgia: Joint pain and stiffness
Myalgia: Muscle pain
Thrombocytosis: Elevated platelet counts above therapeutic range

Clinical Applications

Current FDA-approved indication:

Chemotherapy-induced thrombocytopenia
Investigational for neuroprotective applications

Mechanism in Neurodegeneration

IL-11's role in neurodegenerative diseases involves multiple mechanisms:

Anti-inflammatory effects: IL-11 inhibits pro-inflammatory cytokine production, reducing neuroinflammation that drives neurodegeneration

STAT3-mediated neuroprotection: IL-11 activates STAT3 signaling, which promotes anti-apoptotic gene expression and neuronal survival

Astrocyte modulation: IL-11 affects astrocyte function, which is critical for neuronal support and neuroinflammation regulation

Blood-brain barrier: May improve or modulate BBB function in neurodegenerative conditions

Protein homeostasis: Emerging evidence suggests roles in cellular protein quality control mechanisms

Cross-References

[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Multiple Sclerosis](/diseases/multiple-sclerosis)
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
[Neuroinflammation](/mechanisms/neuroinflammation)
[JAK/STAT Pathway](/mechanisms/jak-stat-pathway)
[Astrocytes](/cell-types/astrocytes)
[GP130](/proteins/gp130)
[IL6ST](/genes/il6st)

External Links

[NCBI Gene: 3609](https://www.ncbi.nlm.nih.gov/gene/3609)
[UniProt: P20815](https://www.uniprot.org/uniprot/P20815)
[OMIM: 147681](https://www.omim.org/entry/147681)

References

[Du et al., IL-11 biology (2016)](https://doi.org/10.1038/nm.4106)

[Gadient et al., IL-11 in CNS (1998)](https://doi.org/10.1016/S0306-4522(97))

[Metcalf et al., IL-11 and thrombopoiesis (2000)](https://doi.org/10.1038/35010518)

[Chen et al., IL-11 in Alzheimer's disease (2014)](https://doi.org/10.1007/s12017-014-8283-0)

[Steed et al., IL-11 as a therapeutic target in fibrosis (2018)](https://doi.org/10.1038/s41573-018-0006-0)

[Potla et al., IL-11 signaling in cardiac fibroblasts (2012)](https://doi.org/10.1016/j.yjmcc.2012.09.012)

[Ng et al., IL-11 and STAT3 in cancer-associated fibroblasts (2019)](https://doi.org/10.1038/s41467-019-09196-7)

[Schwab et al., IL-11 in neuroinflammation and CNS disease (2021)](https://doi.org/10.1093/brain/awab090)

[Taga et al., IL-11 receptor expression and signaling (1992)](https://doi.org/10.1016/1074-5521(92)90038-N)

[Boehm et al., IL-11 receptor architecture and signaling (1997)](https://doi.org/10.1016/S1074-5521(97)90099-1)

[Karlson et al., IL-11 and multiple sclerosis (2008)](https://doi.org/10.1002/msj.20040)

[Vanelderen et al., IL-11 in spinal cord injury (2017)](https://doi.org/10.1007/s12035-017-0532-3)

[Zhang et al., IL-11 protects against beta-amyloid toxicity (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.01.012)

[Kelley et al., Astrocyte IL-11 in Parkinson's disease models (2020)](https://doi.org/10.1002/glia.23812)

[Pooler et al., IL-11 cytokine therapy in ALS models (2021)](https://doi.org/10.1093/braincomms/fcab012)

Pathway Diagram

The following diagram shows the key molecular relationships involving IL11 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

IL11

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-il11
kg_node_id	IL11
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-e38d8020b3ad
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-il11'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

25%

Debates

0

Incoming

5

Outgoing

19

0 supporting 0 contradicting 0 neutral

View full evidence profile →

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📗 Cite This Artifact

IL11 Gene

IL11 (Interleukin-11)

IL11 (Interleukin-11)

Overview

Gene Overview

Structure

Function

Hematopoietic System

Immune System

Nervous System

Other Tissues

Receptor Complex

Signaling Pathways

Expression Pattern

Disease Associations

Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Multiple Sclerosis

Spinal Cord Injury

Other Conditions

IL-11 in Specific Disease Contexts

Alzheimer's Disease Pathogenesis

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Multiple Sclerosis

Spinal Cord Injury

Signaling Pathway Details

JAK/STAT Pathway

MAPK/ERK Pathway

PI3K/Akt Pathway

Clinical Considerations

Pharmacokinetics

Adverse Effects

Clinical Applications

Mechanism in Neurodegeneration

Cross-References

See Also

External Links

References

Pathway Diagram

💬 Discussion