Abstracts

Rationale: Fever, the cause of febrile seizures (FS), is typically associated with pyrogenic inflammatory mediators including lipopolysaccharide and interleukin-1 beta (IL-1β). Whereas these mediators likely contribute to the fever itself, their role in provoking febrile seizures and potentially their consequences, is unclear. Using mice lacking interleukin 1 receptor type I (IL1-RI), we have previously demonstrated that IL-1β contributes critically to fever-induced hyperexcitability underlying experimental febrile seizures. However, the induction of endogenous IL-1β, and the type of cells involved in the synthesis of this mediator have not been clarified. Methods: Immunocytochemistry for IL-1β, together with markers of neurons (NeuN), of astrocytes (GFAP), and of microglia (OX42) was employed to determine the expression of IL-1β at 6 and 24 hours after the onset of experimental FS. In addition, gene array was used to examine for mRNA expression of IL-1β and related inflammatory mediators in hippocampus at 3, 7 and 30 days after the seizures. Results: At the protein level, IL-1β expression was never noted in immature control rats (postnatal days 10-12). After experimental FS, IL-1β expression was found in astrocytes in hippocampus, amygdala and cortex. This expression was associated with increased GFAP expression, and structural changes in the appearance of the astrocytes. Remarkably, IL-1β expression was not induced by stronger seizures, induced by kainic acid in immature rats of the same age. At the mRNA level, IL-1β expression in hippocampus was up-regulated by 3 days after FS and remained elevated for up to a month. Conclusions: Experimental FS provoke expression of IL-1β and associated inflammatory mediators. These data are consistent with some, but not all, studies in children with FS. In addition, inflammatory response may distinguish FS from other seizures induced during development. The possibility that the enduring up-regulation of IL-1β contributes to epileptogenesis following prolonged FS will be explored. Supported by NIH NS 35439 (TZB).