Immune Dysregulation in Depression and Anxiety: A Review of the Immune Response in Disease and Treatment
Abstract
1. Introduction
2. Inflammation
Inflammation, Immune Cells, and Brain Health
3. Dysregulation in General Anxiety Disorder and Depression
3.1. General Anxiety Disorder
3.2. Depression
4. Anti-Inflammatory Effects of Antidepressants
4.1. SSRIs and SNRIs
4.2. MAOIs
4.3. NDRI
4.4. Tricyclic Antidepressants
5. Non-Prescription Medicine
5.1. Nonsteroidal Anti-Inflammatory Drugs
5.2. Palmitoylethanolamide
5.3. Omega-3
5.4. Cannabidiol
5.5. N-Acetylcysteine
6. Non-Pharmaceutical Interventions
6.1. Psychosocial Therapies
6.2. Mindfulness-Based Techniques
6.3. Neuronal Signaling and Brain Stimulation Therapies
7. Limitations
8. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Immune System Mediators | ||
---|---|---|
Classification | Key Functions in Immune Response and Inflammation | |
IL-1β | Pro-inflammatory Cytokine | Promotes fever, leukocyte activation, and acute inflammation; involved in neuroinflammation and chronic disease progression. |
IL-2 | Pro-inflammatory Cytokine | Stimulates T-cell proliferation, enhances immune response, and supports regulatory T-cell function. |
IL-4 | Anti-inflammatory Cytokine | Induces Th2 cell differentiation, promotes antibody class switching to IgE, and inhibits macrophage activation. |
IL-5 | Anti-inflammatory Cytokine | Stimulates eosinophil proliferation and activation, playing a key role in allergic inflammation. |
IL-6 | Pro-inflammatory Cytokine | Mediates acute-phase response, fever, and B-cell activation; can have both pro- and anti- inflammatory effects. |
IL-8 | Chemokine (CXCL8) | Recruits neutrophils to inflammation sites, promotes angiogenesis, and enhances tissue remodeling. |
IL-10 | Anti-inflammatory Cytokine | Suppresses pro-inflammatory cytokine production, regulates immune response, and promotes tolerance. |
IL-12 | Pro-inflammatory Cytokine | Enhances NK- and T-cell cytotoxic activity, promotes Th1 differentiation, and stimulates IFN-γ production. |
IL-12p40 | Cytokine Subunit | Component of IL-12 and IL-23; regulates Th1 and Th17 immune responses and influences inflammation. |
IL-13 | Anti-inflammatory Cytokine | Supports Th2 responses, regulates mucus production, and suppresses macrophage pro-inflammatory activity. |
IL-16 | Chemokine-like Cytokine | Acts as a chemoattractant for CD4+ T-cells, promotes immune cell migration, and regulates inflammation. |
IL-17 | Pro-inflammatory Cytokine | Drives Th17 responses, promotes neutrophil recruitment, and plays a role in autoimmune diseases. |
IL-18 | Pro-inflammatory Cytokine | Enhances IFN-γ production, stimulates NK- and T-cell activity, and amplifies inflammatory responses. |
TNF-α | Pro-inflammatory Cytokine | Induces fever, apoptosis, and systemic inflammation; plays a major role in chronic inflammatory diseases. |
CRP | Acute-phase Protein | Produced in response to IL-6; marker of systemic inflammation and predictor of cardiovascular risk. |
TGF-β | Anti-inflammatory Cytokine | Regulates immune tolerance, inhibits pro-inflammatory cytokines, and promotes tissue repair and fibrosis. |
IFN-α | Type I Interferon | Antiviral response mediator, enhances immune surveillance, and modulates T-cell activity. |
IFN-γ | Type II Interferon | Activates macrophages, promotes Th1 differentiation, and enhances antigen presentation. |
NF-κB | Transcription Factor | Regulates inflammatory gene expression, immune cell activation, and responses to stress and infection. |
Microglial Response to Common Neurotransmitters | ||
---|---|---|
Neurotransmitter | Net Effect | Effects |
Acetylcholine | Suppressive | Less responsive to IFN-γ; reduction in free radical generation; decreased LPS-induced TNF-α. |
Norepinephrine | Suppressive | Reduction in IL-6 and TNF-α; free radical attenuation. |
Serotonin | Suppressive | Reduced TNF-α and IL-6 (in vitro). |
Stimulatory | Motility with phagocytosis; NF-κB signaling. | |
Dopamine | Suppressive | Reduction in NF-κB signaling (D1). |
Stimulatory | Increased NF-κB signaling (D2); release of IL-6 and IL-1β; increased chemotaxis. | |
Substance P | Stimulatory | Potentiates LPS activity; chemotaxis; microglial activation. |
General Trends in Immune Mediators in Response to Various Treatments | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
IL-1 | IL-6 | TNF-α | IFN-γ | NF-κB | IL-8 | CRP | IL-10 | IL-4 | IL-5 | IL-13 | |
SSRI/SNRI | ↓ | ↓ | ↓ | ↓ | ↓ * | ↓ | ↓ | ↑ | |||
MAO-I | ↓ | ↓ | ↓ | ↓ ** | ↓ | ↑ | |||||
NDRI | ↓ | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ||||
TCA | ↓ | ↓ | ↑ | ||||||||
NSAID | ↓ | ↓ | |||||||||
PEA | ↓ *** | ||||||||||
Omega-3 | ↓ | ↓ | ↑ | ||||||||
CBD | ↓ | ↓ | ↓ | ||||||||
NAC | ↓ | ↓ | ↓ | ↓ | ↓ | ||||||
CBT | ↓ | ↓ | ↓ | ↑ | |||||||
TMS | ↓ | ↓ | ↓ |
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Hole, C.; Dhamsania, A.; Brown, C.; Ryznar, R. Immune Dysregulation in Depression and Anxiety: A Review of the Immune Response in Disease and Treatment. Cells 2025, 14, 607. https://doi.org/10.3390/cells14080607
Hole C, Dhamsania A, Brown C, Ryznar R. Immune Dysregulation in Depression and Anxiety: A Review of the Immune Response in Disease and Treatment. Cells. 2025; 14(8):607. https://doi.org/10.3390/cells14080607
Chicago/Turabian StyleHole, Christopher, Akash Dhamsania, Cassandra Brown, and Rebecca Ryznar. 2025. "Immune Dysregulation in Depression and Anxiety: A Review of the Immune Response in Disease and Treatment" Cells 14, no. 8: 607. https://doi.org/10.3390/cells14080607
APA StyleHole, C., Dhamsania, A., Brown, C., & Ryznar, R. (2025). Immune Dysregulation in Depression and Anxiety: A Review of the Immune Response in Disease and Treatment. Cells, 14(8), 607. https://doi.org/10.3390/cells14080607