Levels of IL-1β and IL-1ra in Cerebrospinal Fluid of Human Patients after Single and Prolonged Seizures

Abstract

Background: Experimentally induced seizures are associated with increased production of inflammatory cytokines in the nervous system. Elevated cerebrospinal fluid levels of cytokine interleukin-6 (IL-6) have been found after a single generalized seizure in human patients. After prolonged seizures, levels of IL-6 have been shown to be even higher compared with single seizures. In the present study, we determined the levels of proconvulsive IL-1β and anticonvulsive IL-1ra in cerebrospinal fluid after single tonic-clonic seizures as well as after prolonged seizures. Methods: The levels of cytokines were measured using enzyme-linked immunosorbent assay. Results: We found that after single seizures, a slight increase in anticonvulsive IL-1ra levels was found; however, after prolonged partial or recurrent tonic-clonic seizures, the levels of IL-1ra were significantly elevated, together with decreased IL-1β levels. Conclusion: Our results indicate that after severe seizures, the balance between IL-1-type cytokines is changed towards a neuroprotective and anticonvulsive direction with an overproduction of IL-1ra with respect to potentially neurotoxic IL-1β. This reaction may serve as a defense mechanism of the nervous system against excitotoxic neuronal damage.

Increased level of serum interleukin-1 receptor antagonist subsequent to resolution of clinical symptoms in patients with West syndrome

“…One report stated that there are no significant alterations in the IL-1Ra and IL-1β postictal plasma levels and the seizures in 9 of 11 patients in this study were partial seizures [20]. Moreover, after prolonged partial or recurrent tonicclonic seizures but not single tonic-clonic seizures, the IL-1Ra levels in the CSF increased significantly with decreasing IL-1β levels, as observed in samples obtained within 24 h after seizures [9]. Therefore, these results supported the fact that the seizures themselves affect the cytokine levels of IL-1Ra and IL-1β in patients with localization-related epilepsy; furthermore, the timing of blood sampling is also important for accurately determining the cytokine levels.…”

“…Recently, an accurate assessment of the cytokine levels in the inter-to postictal phases was obtained in patients with localization-related epilepsy by employing a video-EEG methodology [7,9,20]. A significant increase in the plasma levels of IL-1Ra was observed post-seizure, and it returned to baseline within 24 h. A slightly greater increase in the IL-1Ra levels was noted after generalized seizures than after complex partial seizures, but this increase was not significant [7].…”

“…Similarly, the reduction of release of IL-1β by Caspase-1 or interleukin Converting Enzyme inhibitors resulted in anticonvulsant effects [4,5]. In humans, the levels of IL-1β and IL-1Ra are increased in the serum or plasma after seizures [6][7][8][9]. Moreover, immunocytochemical analysis revealed that IL-1β and IL-1Ra were expressed in the cortical tissue of patients with intractable epilepsy but not in histologically normal tissue [10,11].…”

Association Between IL1B and SCN1A Polymorphism and Febrile Seizures in Children in Siberia

“…Recent studies show that the differences in the genes that control defensive reactions of the organism can affect the level of production of the encoded proteins and, thereby, the character of immune response. (5) In this regard, a functional polymorphism of cytokine genes is of great interest, since these proteins contribute most to the regulation of immunity, in epilepsy as well. (6)(7)(8) The most frequent causes of differences in gene structure are point mutations, tandem repeats of parts of the gene, and deletions of nucleotides or small gene fragments.…”

“…The mutant fragments of one or several genes, located very close to each other, can be inherited together (coupling) as the result of selective advantages or, more typically, because of the irregularities of meiotic recombination in this chromosomal region. (5)(6)(7) Multiple animal studies have shown that the components of the immune response can play some role in FS pathogenesis.…”