Cytokine-Mediated Neuroinflammation in Epilepsy

Epilepsy is increasingly recognised not only as a disorder of aberrant neuronal excitability but also as a condition driven by sustained neuroinflammatory processes. Seizure activity induces release of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from resident microglia, astrocytes and infiltrating leukocytes. These mediators amplify neuronal hyperexcitability, compromise blood–brain barrier integrity and perpetuate a vicious cycle of recurrent seizures and inflammation. Conversely, anti-inflammatory cytokines including interleukin-10 (IL-10) and fractalkine (CX3CL1) can exert neuroprotective effects by limiting inflammasome activation and glial overactivation. At the molecular level, key signalling cascades such as NF-κB, NLRP3 inflammasome and Nrf2/HO-1 interact to regulate cytokine production, apoptosis and pyroptotic cell death. Understanding the balance between these opposing forces has yielded novel biomarkers for disease severity and points to promising therapeutic avenues. Targeting cytokine signalling holds potential for modifying epileptogenesis, improving seizure control and mitigating comorbidities such as cognitive dysfunction and mood disorders. Given the global burden of epilepsy, interventions aimed at neuroinflammatory pathways may transform patient outcomes and reduce healthcare costs.

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Cytokine-Mediated Neuroinflammation in Epilepsy publication trend

The graph below shows the total number of articles in cytokine-mediated neuroinflammation in epilepsy across all publications each year (not limited to Nature Index journals).

Technical terms

Cytokine: A small secreted protein that mediates intercellular communication in immune and glial networks, driving or resolving inflammation.

Neuroinflammation: A central nervous system immune response characterised by activation of microglia and astrocytes, release of cytokines and disruption of neuronal function.

Epileptogenesis: The progressive process by which a normal brain develops recurrent spontaneous seizures following an initial insult.

Inflammasome: A multiprotein complex that activates inflammatory caspases, leading to maturation of cytokines such as IL-1β and execution of pyroptotic cell death.

Pyroptosis: A lytic form of programmed cell death driven by inflammasome activation, resulting in cell swelling, membrane rupture and further release of pro-inflammatory mediators.

References

1. Conditional Knockout of IL-1R1 in Endothelial Cells Attenuates Seizures and Neurodegeneration via Inhibiting Neuroinflammation Mediated by Nrf2/HO-1/NLRP3 Signaling in Status Epilepticus Model. Molecular Neurobiology (2023).
2. Inhibiting the IRAK4/NF-κB/NLRP3 signaling pathway can reduce pyroptosis in hippocampal neurons and seizure episodes in epilepsy. Experimental Neurology (2024).
3. Expression of Cytokines and Neurodegeneration in the Rat Hippocampus and Cortex in the Lithium-Pilocarpine Model of Status Epilepticus and the Role of Modulation of Endocannabinoid System. International Journal of Molecular Sciences (2023).
4. Interleukin-10 inhibits interleukin-1β production and inflammasome activation of microglia in epileptic seizures. Journal of Neuroinflammation (2019).