RESUMO
Experimental studies suggest that cytokine production may be triggered by seizure activity. Here we determined the levels of interleukin-6 (IL-6) and its soluble receptor components (sIL-6R and sGp130) in CSF and serum from control subjects and patients after different types of seizures. IL-6 levels were increased after seizures, whereas sIL-6R levels were decreased. Interestingly, the levels of IL-6 were strongly increased after recurrent generalized tonic-clonic seizures (GTCS), whereas after single tonic-clonic or prolonged partial seizures IL-6 levels were increased to lesser extent. These results provide further support for a hypothesis of cytokine production induced by seizure activity per se.
Assuntos
Interleucina-6/sangue , Interleucina-6/líquido cefalorraquidiano , Convulsões/imunologia , Convulsões/fisiopatologia , Antígenos CD/sangue , Antígenos CD/líquido cefalorraquidiano , Receptor gp130 de Citocina , Ensaio de Imunoadsorção Enzimática , Humanos , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/líquido cefalorraquidiano , Receptores de Interleucina-6/análiseRESUMO
We have previously shown that IL-6 protein levels are increased in cerebrospinal fluid in humans after recent tonic-clonic seizures with unchanged levels of IL-1beta and TNFalpha. Here we studied the expression of cytokines IL-6, LIF, IL-1beta and TNFalpha and cytokine receptors IL-6R, LIFR and Gp130 in the rat brain after kainic acid-induced status epilepticus using Northern blot analysis and in situ hybridization histochemistry. After seizures, IL-6 mRNA was induced in the hippocampus, cortex, amygdala and meninges, and IL-6R was up-regulated in the hippocampus. LIF was up-regulated in the hippocampus, cortex and meninges after seizures, and LIFR mRNA was induced in the hippocampus and cortex. Gp130 was constitutively expressed in the brain. After seizures, Gp130 transcription was rapidly induced in the meninges. In thalamus, cortex, amygdala and hippocampus Gp130 mRNA was induced in a delayed fashion. IL-1beta transcription was induced in the temporal lobe cortex and thalamus, and TNFalpha in the hippocampus. In general, the cytokine and their receptor mRNA levels were low in intact rat brain, but were induced by seizures. Since IL-6 and LIF transcripts were induced in the meninges after seizures, the protein products of these transcripts may be more readily released in cerebrospinal fluid after seizures. In addition, the activity of IL-6 and LIF signaling pathways may be influenced by increased expression of their receptors after seizures.
Assuntos
Encéfalo/metabolismo , Citocinas/genética , Epilepsia/metabolismo , Neurônios/metabolismo , Receptores de Citocinas/genética , Animais , Encéfalo/fisiopatologia , Contactinas , Epilepsia/induzido quimicamente , Epilepsia/genética , Regulação da Expressão Gênica/fisiologia , Inibidores do Crescimento/genética , Interleucina-1/genética , Interleucina-6/genética , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Linfocinas/genética , Masculino , Moléculas de Adesão de Célula Nervosa/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-6/genética , Receptores de OSM-LIF , Fator de Necrose Tumoral alfa/genéticaRESUMO
Cardiolipin (CL) and ß(2)-Glycoprotein I (ß(2)-GpI) antibodies have been shown to associate with various neurological symptoms including seizures and cognitive dysfunction. Here we studied the prevalence of CL, ß(2)-GpI and antinuclear (ANA) antibodies in 74 patients with various developmental disorders with epilepsy and 70 healthy controls. Developmental disorders were classified into genetic syndromes and diseases, genetic and/or acquired conditions, cortical dysgenesias and acquired encephalopathias. IgM-CL and ß(2)-GpI antibodies were significantly more common in patients (46% vs. 20%, p<0.001 and 10% vs. 0%, p<0.05). Patients with most frequent seizures were more likely to have IgM-CL antibodies. The risk for positive IgM-CL, IgG-CL and ß(2)-GpI antibodies increased concomitantly with increasing intellectual disability. Present data demonstrates that epilepsy with frequently recurring seizures may be associated with secondary immune system activation.
Assuntos
Autoanticorpos/imunologia , Cardiolipinas/imunologia , Transtornos Cognitivos/imunologia , Deficiências do Desenvolvimento/imunologia , Convulsões/imunologia , beta 2-Glicoproteína I/imunologia , Adolescente , Adulto , Anticorpos Antinucleares/imunologia , Anticonvulsivantes/uso terapêutico , Quimioterapia Combinada , Epilepsia/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/análise , Testes de Inteligência , Masculino , Pessoa de Meia-Idade , Convulsões/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: Experimental studies suggest increased cerebral production of inflammatory cytokines after prolonged seizures. Whether a single non-prolonged seizure in human patients is associated with activation of cytokine network is still unknown. MATERIALS AND METHODS: We studied the levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), interlukin-6 (IL-6) and soluble IL-6 receptors (sIL-6R and Gp130) in plasma after single seizures during video-EEG recordings in patients with chronic localization-related epilepsy. RESULTS: The levels of IL-1ra and IL-6 were increased after seizures, whereas IL-1beta and IL-6 cytokine receptors remained unchanged. CONCLUSIONS: These results show that only single seizures cause activation of cytokine cascade and associated inflammatory signals. In the case of recurrent seizures, these signals may result in structural changes in the nervous tissue, which are generally associated with drug refractory epilepsy.