Editorial - Immunology Case Reports (2025) Volume 8, Issue 2

Cytokine Storms in the Brain: Linking Systemic Infections to Neurological Disorders

Ashanty Melo^*

Department of Immunology, Zhejiang University, China

*Corresponding Author:

Ashanty Melo
Department of Immunology,
Zhejiang University,
China
E-mail: Ashanty367@tcd.ie

Received:02-Jan-2025, Manuscript No. AAICR-25-171197; Editor assigned:03-Jan-2025, PreQC No. AAICR-25-171197(PQ); Reviewed:18-Jan-2025, QC No. AAICR-25-171197; Revised:24-Jan-2025, Manuscript No. AAICR-25-171197(R); Published:31-Jan-2025, DOI:10.35841/aaicr-8.2.197

Citation: Melo A. Cytokine storms in the brain: Linking systemic infections to neurological disorders. Immunol Case Rep. 2025;8(2):197

Introduction

Systemic infections, particularly those caused by viruses, can trigger an overwhelming immune response known as a cytokine storm. While this hyperinflammatory state is primarily associated with peripheral organ damage, emerging evidence reveals its profound impact on the central nervous system (CNS). Cytokine storms can disrupt the blood-brain barrier (BBB), activate resident immune cells, and induce neuroinflammation, leading to a spectrum of neurological disorders. Systemic infections that provoke cytokine storms may act as environmental triggers for neurodegeneration, especially in genetically predisposed individuals. This underscores the importance of monitoring and managing neuroinflammation in patients recovering from severe infections. Understanding the mechanisms by which systemic infections provoke cytokine storms in the brain is crucial for developing targeted therapies and mitigating long-term neurological consequences [1].

A cytokine storm is an excessive and uncontrolled release of pro-inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). This immune overreaction can result in widespread tissue damage, organ failure, and death. In the context of viral infections like SARS-CoV-2, Ebola, and influenza, cytokine storms have been implicated in severe disease progression and complications beyond the primary site of infection [2].

The brain is traditionally considered an immune-privileged organ, protected by the BBB. However, systemic inflammation can compromise this barrier, allowing peripheral cytokines and immune cells to infiltrate the CNS. Once inside, these molecules activate microglia—the brain’s resident immune cells—leading to a cascade of neuroinflammatory responses. This neuroinflammation can disrupt neuronal signaling, induce oxidative stress, and promote apoptosis, contributing to acute and chronic neurological symptoms. The brain’s limited capacity for regeneration makes it particularly vulnerable to sustained inflammatory insults [3].

The COVID-19 pandemic has highlighted the neurological impact of cytokine storms. SARS-CoV-2 infection is associated with a wide range of CNS symptoms, including headache, encephalopathy, stroke, and cognitive impairment. Studies have detected viral RNA in cerebrospinal fluid and brain tissue, suggesting direct neuroinvasion. However, many neurological complications arise in the absence of detectable virus in the CNS, implicating systemic cytokine-mediated mechanisms. Elevated levels of IL-6 and IL-1β have been correlated with severe neurological outcomes in COVID-19 patients. These cytokines can disrupt BBB integrity and promote neuroinflammation, leading to encephalitis and long-term cognitive deficits [4].

Cytokines increase BBB permeability, allowing immune cells and inflammatory mediators to enter the CNS. Peripheral cytokines activate microglia, which release additional pro-inflammatory molecules and exacerbate neuronal damage. Chronic neuroinflammation triggered by cytokine storms may increase the risk of neurodegenerative diseases. For example, sustained IL-1β elevation has been linked to dopaminergic neuron loss in Parkinson’s disease models. Similarly, TNF-α and IL-6 are implicated in Alzheimer’s disease pathology, promoting amyloid-beta accumulation and tau phosphorylation. Inflammatory responses generate reactive oxygen species (ROS), damaging neurons and glial cells. Cytokine-induced glutamate release can overstimulate neurons, leading to cell death. These mechanisms collectively contribute to the development of neurological disorders such as encephalopathy, seizures, and neurodegeneration [5].

Conclusion

Cytokine storms represent a critical link between systemic infections and neurological disorders. By breaching the brain’s defenses and triggering neuroinflammation, these immune overreactions can cause acute symptoms and contribute to chronic neurodegeneration. As emerging pathogens continue to challenge global health, understanding and mitigating the neurological impact of cytokine storms will be essential for comprehensive patient care and long-term recovery.

References

1. Meng W, Hao Y, He C, et al. Exosome-orchestrated hypoxic tumor microenvironment. Mol Cancer. 2019;18(2):5-7.

Indexed at, Google Scholar, Cross Ref

2. Garnier D, Magnus N, Meehan B, et al. Qualitative changes in the proteome of extracellular vesicles accompanying cancer cell transition to mesenchymal state. Exp Cell Res. 2013;319(17):2747-57.

Indexed at, Google Scholar, Cross Ref

3. Thorburn J, Andrysik Z, Staskiewicz L, et al. Autophagy controls the kinetics and extent of mitochondrial apoptosis by regulating PUMA levels. Cell Rep. 2014;7(1):45–52.

Indexed at, Google Scholar, Cross Ref

4. Ichim G, Lopez J, Ahmed SU, et al. Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death. Mol. Cell. 2015;57(5):860-72.

Indexed at, Google Scholar, Cross Ref

5. Mulcahy Levy JM, Thorburn A. Autophagy in cancer: moving from understanding mechanism to improving therapy responses in patients. Cell Death Differ. 2020;27:843-57.

Indexed at, Google Scholar, Cross Ref