Immunology Case Reports

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.
Reach Us +1 (202) 780-3397

Editorial - Immunology Case Reports (2025) Volume 8, Issue 3

Peripheral Immune Activation and Its Impact on Cognitive Function

Irfan Saline *

Department of Microbiology, University of Bristol, United Kingdom

*Corresponding Author:
Irfan Saline
Department of Microbiology,
University of Bristol,
United Kingdom
E-mail: irfans@unm.edu

Received:02-Jan-2025, Manuscript No. AAICR-25-171207; Editor assigned:03-Jan-2025, PreQC No. AAICR-25-171207(PQ); Reviewed:18-Jan-2025, QC No. AAICR-25-171207; Revised:24-Jan-2025, Manuscript No. AAICR-25-171207(R); Published:31-Jan-2025, DOI:10.35841/aaicr-8.3.207

Citation: Saline I. Peripheral immune activation and its impact on cognitive function. Immunol Case Rep. 2025;8(3):207

Visit for more related articles at Immunology Case Reports

Introduction

The immune system and the brain were once thought to operate in isolation, with the central nervous system (CNS) considered immune-privileged. However, mounting evidence reveals a dynamic and bidirectional relationship between peripheral immune activation and cognitive function. Inflammation originating outside the brain can profoundly influence neural circuits, synaptic plasticity, and behavior. This connection has significant implications for understanding neurodegenerative diseases, psychiatric disorders, and the cognitive effects of systemic illness. The immune-brain axis refers to the complex communication network between peripheral immune cells and the CNS. This interaction is mediated through several pathways: Pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 can cross the blood-brain barrier (BBB) or signal through circumventricular organs to influence brain function. The vagus nerve transmits immune signals from the periphery to the brainstem, modulating neuroinflammatory responses. Circulating immune mediators can affect endothelial cells of the BBB, altering permeability and triggering neuroinflammation. These mechanisms allow peripheral immune activation to influence brain physiology even in the absence of direct infection or injury [1].

Acute peripheral inflammation—such as that caused by infection, surgery, or trauma—can lead to transient cognitive impairments. This phenomenon, known as “sickness behavior,” includes fatigue, reduced attention, memory deficits, and mood changes. It is driven by cytokine-induced changes in neurotransmitter systems and synaptic function. For example, studies have shown that systemic administration of lipopolysaccharide (LPS), a bacterial endotoxin, induces cognitive deficits in rodents by increasing IL-1β levels in the hippocampus, a region critical for learning and memory. Persistent peripheral inflammation is increasingly recognized as a risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and vascular dementia. Chronic immune activation can lead to: Peripheral cytokines sensitize microglia, the brain’s resident immune cells, to overreact to subsequent insults. Sustained inflammation compromises BBB integrity, allowing immune cells and toxins to enter the brain. In AD, systemic inflammation accelerates amyloid-beta deposition and tau phosphorylation, contributing to cognitive decline [2].

Epidemiological studies have linked elevated peripheral markers like C-reactive protein (CRP) and IL-6 to increased dementia risk. Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) are associated with cognitive dysfunction. These impairments may result from: Circulating autoantibodies that cross the BBB and target neuronal structures. Chronic cytokine exposure, which alters neurotransmission and neuroplasticity. Medication effects, including corticosteroids and immunosuppressants. In SLE, neuropsychiatric symptoms—including memory loss and executive dysfunction—are common and correlate with disease activity and inflammatory markers [3].

The gut microbiota plays a pivotal role in modulating peripheral immunity and, by extension, cognitive function. Dysbiosis—an imbalance in microbial composition—can lead to systemic inflammation and altered brain signaling. Mechanisms include: Studies have shown that probiotic supplementation can improve cognitive performance in patients with mild cognitive impairment, suggesting a therapeutic role for microbiota modulation. Aging is accompanied by a low-grade, chronic inflammatory state known as “inflammaging.” This condition is characterized by elevated levels of pro-inflammatory cytokines and immune dysregulation.  Older adults with higher systemic inflammation show faster rates of cognitive decline and poorer performance on memory and executive function tests [4].

Peripheral inflammation is also implicated in psychiatric conditions such as depression, schizophrenia, and bipolar disorder. Elevated cytokines can: Anti-inflammatory treatments, including NSAIDs and cytokine inhibitors, have shown promise in alleviating cognitive symptoms in these disorders. Understanding the impact of peripheral immune activation on cognition opens new therapeutic avenues: Peripheral inflammatory markers may serve as early indicators of cognitive decline and guide personalized interventions. These strategies highlight the importance of systemic health in maintaining cognitive resilience [5].

Conclusion

Peripheral immune activation is a powerful modulator of cognitive function, influencing brain health across the lifespan and in various disease states. From acute infection to chronic inflammation, the immune system communicates with the brain through intricate pathways that shape behavior, memory, and executive function. As research continues to unravel these connections, integrating immunological insights into cognitive care will be essential for preventing and treating neuropsychiatric and neurodegenerative disorders.

References

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

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. Indexed at, Google Scholar, Cross Ref

Get the App