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Epilepsia. 2005 Dec;46(12):1906-13.

Causal links between brain cytokines and experimental febrile convulsions in the rat.

Author information

1
Hotchkiss Brain Institute, Department of Physiology and Biophysics, Faculty of Medicine University of Calgary, Calgary, Alberta, Canada. jgheida@ucalgary.ca

Abstract

PURPOSE:

Despite the prevalence of febrile convulsions (FCs), their pathophysiology has remained elusive. We tested the hypothesis that components of the immune response, particularly the proinflammatory cytokine interleukin-1beta (IL-1beta) and its naturally occurring antagonist interleukin-1 receptor antagonist (IL-1ra) may play a role in the genesis of FC.

METHODS:

Postnatal day 14 rats were treated with lipopolysaccharide (LPS; 200 microg/kg, i.p.) followed by a subconvulsant dose of kainic acid (1.75 mg/kg, i.p.). Brains were harvested at and 2 h after onset of FCs to measure brain levels of IL-1beta and IL-1ra. Separate groups of animals were given intracerebroventricular (ICV) injections of IL-1beta, or IL-1ra in an attempt to establish a causal relation between the IL-1beta/IL-1ra system and FCs.

RESULTS:

Animals with FCs showed increased IL-1beta in the hypothalamus and hippocampus but not in the cortex compared with noFC animals that also received LPS and kainic acid. This increase was first detected in the hippocampus at onset of FCs. No detectable difference in IL-1ra was found in brain regions examined in either group. When animals were treated with IL-1beta ICV, a dose-dependant increase was noted in the proportion of animals that experienced FCs, whereas increasing doses of IL-1ra, given to separate groups of animals, were anticonvulsant.

CONCLUSIONS:

Our results suggest that excessive amounts of IL-1beta may influence the genesis of FCs. This may occur by overproduction of IL-1beta, or by alteration in the IL-1beta/IL-1ra ratio in the brain after an immune challenge.

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