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

Kan, Anne A; de Jager, Wilco; de Wit, Marina; Heijnen, Cobi; van Zuiden, Mirjam; Ferrier, Cyrill; van Rijen, Peter; Gosselaar, Peter; Hessel, Ellen; van Nieuwenhuizen, Onno; de Graan, Pierre N E

doi:10.1186/1742-2094-9-207

Journal of Neuroinflammation

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	[50–53]
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.	[57–60]
				- 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.	[70–72]	IFNα	- Suppression of hippocampal CA1 neurons & LTP	[73, 74]
IL-1α	Polymorphisms that lead to increased transcription are associated with TLE	[75–77]	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	[83–85]
				- reduces hippocampal excitability
	- Higher levels correlate with increased SRS after eFS
IL-5	- Implicated in BBB disruption in CNS tumor bloodvessels	[86–88]	IL-5	- Anti-inflammatory actions in the periphery as a Th2 cytokine	[87–89]
	- 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]

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.

Back to article page

ISSN: 1742-2094

Contact us

Submission enquiries: journalsubmissions@springernature.com