The role of cytokines in the pathophysiology of epilepsy.
Recent findings in experimental models and in the clinical setting highlight the possibility that inflammatory processes in the brain contribute to the etiopathogenesis of seizures and to the establishment of a chronic epileptic focus. Prototypical inflammatory cytokines such as IL-1 beta, TNF-alpha and IL-6 have been shown to be overexpressed in experimental models of seizures in brain areas of seizure generation and propagation, prominently by glia and to a lesser extent by neurons. Cytokines receptors are also upregulated, and the related intracellular signalling is activated, in both cell populations highlighting autocrine and paracrine actions of cytokines in the brain. Cytokines have been shown to profoundly affect seizures in rodents; in particular, IL-1 beta is endowed of proconvulsant activity in a large variety of seizure models. The recent demonstration of functional interactions between cytokines and classical neurotransmitters such as glutamate and GABA, suggest the possibility that these interactions underlie the cytokine-mediated changes in neuronal excitability, thus promoting seizure phenomena and the associated neuropathology. These findings point out at novel glio-neuronal communications in diseased conditions and highlight potential new targets for therapeutic intervention.
Vezzani
Annamaria
A
Mario Negri Institute for Pharmacological Research, Department of Neuroscience, Via G La Masa, 19 Milano, Italy. vezzani@marionegri.it
Balosso
Silvia
S
Ravizza
Teresa
T
D000818:Animals; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology
D016207:Cytokines; D053583:Interleukin-1beta; D018377:Neurotransmitter Agents