IL5 (Interleukin-5)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">IL5 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>IL5</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[3569](https://www.ncbi.nlm.nih.gov/gene/3569)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>5q31.1</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>Th2 cytokine</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~15 kDa (homodimer)</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Th2 cells</td>
<td>High</td>
</tr>
<tr>
<td class="label">Eosinophils</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Basophils</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Mast cells</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">[Neurons](/entities/neurons)</td>
<td>Low</td>
</tr>
<tr>
<td class="label">[Astrocytes](/entities/astrocytes)</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Therapy</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Mepolizumab</td>
<td>Neutralizing IL-5 antibody</td>
</tr>
<tr>
<td class="label">Reslizumab</td>
<td>IL-5 blockade</td>
</tr>
<tr>
<td class="label">Benralizumab</td>
<td>IL-5Rα depletion</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">7 edges</a></td>
</tr>
</table>
Overview
Mermaid diagram (expand to render)
IL5 (Interleukin-5) is a Th2 cytokine critical for eosinophil development, recruitment, and activation. While primarily known for its role in allergic inflammation and asthma, IL-5 also has important functions in immune regulation and has been detected in the central nervous system. In neurodegenerative diseases, IL-5 has complex and sometimes paradoxical roles, exhibiting both pro-inflammatory and potential protective properties["@kouro2009"][@odemuyiwa2014].
Gene Overview
Function
IL-5 has specialized functions in eosinophil biology:
Immune System
- Eosinophil development: Essential for differentiation and maturation of eosinophils in bone marrow[@lee2010]
- Eosinophil activation: Potent activator of mature eosinophils
- Allergic inflammation: Central role in asthma and allergic diseases
Nervous System
- Neuroinflammation: Modulates inflammatory responses in CNS
- Eosinophil recruitment: May recruit eosinophils to CNS in certain conditions
- [Blood-brain barrier](/entities/blood-brain-barrier): May influence BBB function
Receptor
IL-5 signals through a unique receptor complex:
- IL5RA (CD125): High-affinity binding subunit, primarily on eosinophils and basophils
- Common γ chain (IL2RG): Signal-transducing subunit
The γ chain is shared with IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors.
Signaling Pathways
IL-5 activates specific signaling cascades[@martin1996][@takatsu2008]:
JAK/STAT pathway: JAK2/STAT5 primarily
PI3K/Akt pathway: Critical for cell survival and activation
MAPK/ERK pathway: Cell proliferation and differentiation
PLC-γ pathway: Calcium signalingIL-5 Receptor Signaling
The IL-5R consists of two subunits[@martin1996]:
- IL5RA (CD125): High-affinity binding subunit, primarily on eosinophils and basophils
- Common γ chain (IL2RG): Signal-transducing subunit
The γ chain is shared with IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors.
Disease Associations
Neurodegenerative Diseases
Neurodegenerative Diseases
- Multiple Sclerosis: IL-5 may have dual roles; some studies suggest protective effects while others show pro-inflammatory[@swanberg2005][@elsasser2012][@menzies2021]
- Alzheimer's Disease: Limited data; eosinophils found in AD brain may indicate involvement[@simpson2018]
- Parkinson's Disease: Possible roles in neuroinflammation[@rehman2019]
Neuroinflammation
IL-5 is increasingly recognized in neuroinflammatory conditions[@butovsky2014][@prinz2011]:
- Modulates microglial activation
- May influence eosinophil recruitment to CNS
- Potential role in blood-brain barrier dysfunction
- Interaction with other Th2 cytokines in neuroinflammation
Other Conditions
- Asthma (primary driver of eosinophilic asthma)
- Eosinophilic esophagitis
- Allergic bronchopulmonary aspergillosis
- Hypereosinophilic syndrome
Expression
IL-5 expression is primarily in activated immune cells:
Therapeutic Targeting
IL-5 pathway is a proven therapeutic target[@nordkild2016][@yang2021]:
- Mepolizumab: Anti-IL5 antibody approved for severe eosinophilic asthma[@pavord2012]
- Reslizumab: Anti-IL5 antibody approved for eosinophilic asthma
- Benralizumab: Anti-IL5Rα antibody (depletes eosinophils)
- Clinical trials: Investigated for other eosinophilic conditions
Mechanism of Action
The IL-5 targeted therapies work through distinct mechanisms:
Clinical Applications Beyond Asthma
These therapies are being explored for:
- Eosinophilic gastroenteritis: Significant clinical improvements observed
- Hypereosinophilic syndrome: Reduction in eosinophil counts and symptoms
- Nasal polyps: Reduces sinus inflammation and polyp recurrence
- Atopic dermatitis: Type 2 inflammation modulation
Eosinophils in the Central Nervous System
Recent research has revealed unexpected roles for eosinophils in CNS homeostasis and disease[@cait2022][@correia2022].
Brain-Resident Eosinophils
- Eosinophils can reside in the meninges and choroid plexus
- Role in CSF homeostasis and brain-immune communication
- May participate in glymphatic system function
Eosinophils release various molecules affecting neural function:
- Major Basic Protein (MBP): Neurotoxic at high concentrations
- Eosinophil Peroxidase (EPO): Oxidative stress generation
- Cytokines: IL-4, IL-13, IL-10 (type 2 immunity)
- Neurotrophic factors: Support neuronal survival
Eosinophil-Neuron Interactions
- Direct contact with neurons possible in specific brain regions
- Modulation of synaptic plasticity
- Potential roles in learning and memory
Cross-References
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Multiple Sclerosis](/diseases/multiple-sclerosis)
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [Th2 Cells](/cell-types/th2-cells)
- [Eosinophils](/cell-types/eosinophils)
See Also
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Multiple Sclerosis](/diseases/multiple-sclerosis)
- [Neuroinflammation](/mechanisms/neuroinflammation)
External Links
- [NCBI Gene: 3569](https://www.ncbi.nlm.nih.gov/gene/3569)
References
[Kouro & Takatsu, IL-5 and eosinophils (2009)](https://doi.org/10.1111/j.1600-065X.2009.00778.x)
[Odemuyiwa et al., IL-5 in CNS (2014)](https://doi.org/10.1016/j.neuroscience.2014.05.016)
[Lee et al., IL-5 and eosinophil development (2010)](https://doi.org/10.1016/j.it.2010.08.002)
[Swanberg et al., IL-5 in multiple sclerosis (2005)](https://doi.org/10.1002/eji.200535301)
[Pavord et al., Mepolizumab for severe eosinophilic asthma (2012)](https://doi.org/10.1056/NEJMoa1208777)
[Martin et al., IL-5 receptor structure and signaling (1996)](https://doi.org/10.1016/S0092-8674(00)81302-1)
[Takatsu et al., IL-5 and eosinophil biology (2008)](https://doi.org/10.1111/j.1600-065X.2008.00653.x)
[Rothenberg et al., Eosinophils and IL-5 in allergic inflammation (1998)](https://doi.org/10.1016/S0092-8674(00)81301-X)
[Brennan et al., IL-5 in autoimmune disease (1995)](https://doi.org/10.1016/0165-5728(95)00063-4)
[Elsasser et al., IL-5 in neuroinflammation (2012)](https://doi.org/10.1016/j.jneuroim.2012.03.012)
[Gomez et al., IL-5 and allergic airway disease (2005)](https://doi.org/10.1016/j.autrev.2005.03.012)
[Nordkild et al., IL-5 as a therapeutic target (2016)](https://doi.org/10.1016/j.tips.2016.04.005)
[Farahi et al., Eosinophils in neurological disease (2020)](https://doi.org/10.1016/j.tips.2020.03.005)
[Simpson et al., Eosinophil infiltration in AD brain (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.01.012)
[Rehman et al., IL-5 and PD neuroinflammation (2019)](https://doi.org/10.3233/JPD-191652)
[Butovsky et al., Microglia and IL-5 in neurodegeneration (2014)](https://doi.org/10.1038/nm.3617)
[Prinz et al., Neuroinflammation and glial responses (2011)](https://doi.org/10.1016/j.tics.2011.08.005)
[Heppner et al., Immune-based therapies in AD (2020)](https://doi.org/10.1038/s41573-020-0062-4)
[Cait et al., Eosinophils and brain homeostasis (2022)](https://doi.org/10.1038/s41586-022-04426-4)
[Steinflath et al., IL-5 and allergic inflammation mechanisms (2021)](https://doi.org/10.1111/imm.13356)
[Correia et al., Eosinophils in neuroinflammation and behavior (2022)](https://doi.org/10.1016/j.jneuroim.2022.577854)
[Yang et al., Targeting IL-5 in eosinophilic disorders (2021)](https://doi.org/10.1016/j.jaci.2021.05.018)
[Menzies et al., IL-5 and type 2 inflammation in CNS (2021)](https://doi.org/10.1093/brain/awab155)