Functional role of proinflammatory and anti-inflammatory cytokines in seizures

Advances in Experimental Medicine and Biology
Annamaria VezzaniMaria G De Simoni

Abstract

Recent evidence has shown that proinflammatory and anti-inflammatory molecules are synthesized during epileptic activity in glial cells in CNS regions where seizures initiate and spread. These molecules are released and interact with specific receptors on neurons. Since various cytokines have been shown to affect neuronal excitability, this led to the hypothesis that they may have a role in altering synaptic transmission in epileptic conditions. Indeed, intracerebral application of IL-1beta enhances epileptic activity in experimental models while its naturally occurring receptor antagonist (IL-1Ra) mediates anticonvulsant actions. Transgenic mice overexpressing IL-1Ra in astrocytes are less susceptible to seizures, indicating that endogenous IL-1 has proconvulsant activity. Several studies indicate a central role of IL-1beta for the exacerbation of brain damage after ischemic, traumatic or excitotoxic insults, suggesting that it may also contribute to neuronal cell injury associated with seizures. Finally, a functional polymorphism in the IL-1beta gene promoter, possibly associated with enhanced ability to produce this cytokine, has been specifically found in temporal lobe epilepsy patients with hippocampal sclerosis and in chi...Continue Reading

Citations

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