Seizure susceptibility to various convulsant stimuli of knockout interleukin-6 mice.

In the present study, the susceptibility of knockout interleukin-6 (IL-6(-/-)) mice to various convulsant stimuli has been evaluated and compared with other three related mice strains. Animals were treated with chemical convulsants impairing the gamma-aminobutyric acid neurotransmission [pentylenetetrazole (PTZ), picrotoxin, bicuculline, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), methyl-beta-carboline-3-carboxylate (beta-CCM)], enhancing glutamatergic neurotransmission [N-methyl-d-aspartate (NMDA), alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainic acid (KA)] or a K(+)channel blocker [4-aminopyridine (4-AP)]. The behavioural changes of such convulsant stimuli on IL-6(-/-) were observed and compared with those observed in C57, IL-6(+/+) and DBA/2 mice. The occurrence of clonic and/or tonic seizures was scored and statistically analysed to observe possible differences on seizure susceptibility. The IL-6(-/-) mice exhibited significantly higher seizure susceptibility to PTZ, beta-CCM, DMCM, NMDA, AMPA and KA than did the other mice strains, with the exception of DBA/2 mice. This study demonstrates that IL-6(-/-) mice possess an increased susceptibility to some convulsant stimuli. In particular, the major convulsant effects produced by NMDA, AMPA and KA suggest that the excitatory amino acid system is more active in the central nervous system (CNS) of IL-6(-/-) mice. The present data suggest that IL-6(-/-) mice might be a valid novel epileptic model for the study of pathophysiology and pharmacology of epileptic seizures.