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

Giovambattista De Sarro1, Emilio Russo, Guido Ferreri

  • 1Department of Experimental and Clinical Medicine "G. Salvatore", School of Medicine, University of Catanzaro, Policlinico Mater Domini, Via T. Campanella, 115, 88100 Catanzaro, Italy. desarro@unicz.it

Pharmacology, Biochemistry, and Behavior
|April 22, 2004
PubMed

Insights

Mice lacking interleukin-6 (IL-6(-/-)) show increased seizure susceptibility to various chemical convulsants, particularly those affecting glutamatergic neurotransmission. These findings suggest IL-6(-/-) mice may serve as a novel model for epilepsy research.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Interleukin-6 (IL-6) is a cytokine involved in immune responses and inflammation.
  • Its role in neurological conditions, including epilepsy, is not fully understood.
  • Understanding IL-6's impact on seizure susceptibility is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To evaluate the seizure susceptibility of interleukin-6 knockout (IL-6(-/-)) mice.
  • To compare the response of IL-6(-/-) mice to various convulsant stimuli against other mouse strains.
  • To investigate the potential of IL-6(-/-) mice as an animal model for epilepsy research.

Main Methods:

  • Administered various chemical convulsants to IL-6(-/-) mice and control strains (C57, IL-6(+/+), DBA/2).
  • Tested convulsants targeting gamma-aminobutyric acid (GABA) and glutamatergic neurotransmission, as well as a K(+) channel blocker.
  • Observed and statistically analyzed behavioral changes, specifically the occurrence and severity of clonic and tonic seizures.

Main Results:

  • IL-6(-/-) mice exhibited significantly higher seizure susceptibility to pentylenetetrazole (PTZ), methyl-beta-carboline-3-carboxylate (beta-CCM), methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), N-methyl-d-aspartate (NMDA), alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainic acid (KA).
  • This heightened susceptibility was observed in comparison to C57 and IL-6(+/+) mice, but not DBA/2 mice.
  • The pronounced effects of NMDA, AMPA, and KA suggest enhanced excitatory amino acid system activity in the central nervous system (CNS) of IL-6(-/-) mice.

Conclusions:

  • IL-6(-/-) mice demonstrate increased susceptibility to certain convulsant stimuli.
  • The results indicate a potential role for IL-6 in modulating neuronal excitability.
  • IL-6(-/-) mice represent a promising novel model for studying the pathophysiology and pharmacology of epileptic seizures.

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