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 mechanismsCross-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)
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Multiple Sclerosis](/diseases/multiple-sclerosis)
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [JAK/STAT Pathway](/mechanisms/jak-stat-pathway)
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)