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Table 6 Summary of potential pro-and anti-epileptogenic properties of inflammatory mediators

From: Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines

“Pro-epileptogenic” “Anti-epileptogenic”
Protein Function in CNS reference Protein Function in CNS reference
CCL2 - contributes to immune-cell recruitment across the BBB [49] IL-1ra - An anti-infllammatory protein with seizure inhibiting properties in experimental TLE [5053]
CCL3 - Capable of inducing Ca2+ transients in neuronal and microglial cultures. [22, 54] IL-7 Neurotrophic actions in embryonic brain cultures [55, 56]
  - Inhibition of systemic receptor leads to decrease in seizure activity     
CCL4 - Capable of inducing Ca2+ transients in neuronal and microglial cultures. [22, 54] IL-10 - Inhibits development of seizures in FS and a hypoxia model for epilepsy. [5760]
     - SNPs that result in increased IL-10 are decreased in FS patients.  
  - Inhibition of systemic receptor leads to decrease in seizure activity     
     -Can give trophic support to neurons  
CCL5 - Capable of inducing Ca2+ transients in neuronal and microglial cultures [22, 49, 54, 61] IL-13 - Protects BBB integrity. [62]
  - Glut release from CNS cells in hypothalamus     
  - contributes to immune-cell recruitment across the BBB     
  - Inhibition of systemic receptor leads to decrease in seizure activity     
CCL19 immune-cell recruitment across the BBB. [63, 64] IL-25 - Protects BBB integrity [62, 65]
CCL22 -Immune-cell recruitment across the BBB. [66, 67] IL-27 Marked anti-inflammatory actions in EAE. [68, 69]
CXCL9 -Immune-cell recruitment across the BBB. [7072] IFNα - Suppression of hippocampal CA1 neurons & LTP [73, 74]
IL-1α Polymorphisms that lead to increased transcription are associated with TLE [7577] HGF - Enhances neuronal survival [78, 79]
IL-1β - Increased NMDA R subunit NR2B phosphorylation leading to increased Ca2+ influx [80],[25, 52, 81, 82] VEGF - neuroprotective after experimental seizures [8385]
     - reduces hippocampal excitability  
  - Higher levels correlate with increased SRS after eFS     
IL-5 - Implicated in BBB disruption in CNS tumor bloodvessels [8688] IL-5 - Anti-inflammatory actions in the periphery as a Th2 cytokine [8789]
  - Induces microglial proliferation     
     - Induces microglial activation  
IL-7 Induces neuronal apoptosis in human NT2 cells [90]    
IL-22 - BBB disruption through down-regulation of occludin. [91]    
VEGF BBB disruption → reduction in tight junction proteins in kainate model for TLE [92, 93].    
ICAM-1 - implicated in BBB disruption [20]    
VCAM-1 - Immune-cell recruitment across the BBB [20]    
  1. Abbreviations: BBB blood brain barrier, CNS central nervous system, SRS spontaneous recurrent seizure activity, NMDA N-methyl D-aspartate, NR2B N-methyl D-aspartate receptor subtype 2B, eFS experimental febrile seizures, NT2 neuronal teratocarcinoma Tera 2, FS febrile seizures, LTP long term potentiation, EAE experimental autoimmune encephalitis, SNP single nucleotide polymorphism.