Effects of interleukin-2 on various models of experimental epilepsy in DBA/2 mice

Neuroimmunomodulation. 1994 Nov-Dec;1(6):361-9. doi: 10.1159/000097189.

Abstract

The effects of interleukin-2 (IL-2) on various models of experimental epilepsy were studied after intracerebroventricular administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. Convulsions were induced by physical stimulus (sound of 109 dB. 12-16 kHz) or by chemical compounds (bicuculline, cephazolin or kainate). The present study demonstrated that human recombinant IL-2 (hr-IL-2) and mouse recombinant IL-2 (mr-IL-2) not only did not antagonize audiogenic seizures in DBA/2 mice but increased the incidence of seizures after the highest doses studied. In addition, hr-IL-2 and mr-IL-2 dose dependently facilitated sound-induced seizures at subthreshold sound exposure (83 dB). Pretreatment with monoclonal rat-antimouse IL-2 antibodies significantly affected the changes of occurrence of audiogenic seizures in DBA/2 mice induced by mr-IL-2. In addition, pretreatment with anti-IL-2 receptor monoclonal antibodies (anti-Tac) was able to completely antagonize or reduce the effects of IL-2 on audiogenic seizures. The effects of mr-IL-2 were also studied in two different models of epilepsy: the bicuculline and cephazolin models, due to impairment of GABAergic transmission, and the kainate model, due to an increase in excitatory amino acid transmission. In all models, mr-IL-2 demonstrated to facilitate the seizures induced by these chemoconvulsants. Since the proconvulsant properties of IL-2 were antagonized by specific monoclonal antibodies, we suggest that some epileptic phenomena may be linked to stimulation of IL-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bicuculline / toxicity
  • Cefazolin / toxicity
  • Convulsants / pharmacology
  • Convulsants / toxicity*
  • Electroencephalography / drug effects
  • Epilepsy, Tonic-Clonic / chemically induced*
  • Epilepsy, Tonic-Clonic / etiology
  • Epilepsy, Tonic-Clonic / genetics
  • Epilepsy, Tonic-Clonic / physiopathology
  • Injections, Intraventricular
  • Interleukin-2 / pharmacology
  • Interleukin-2 / toxicity*
  • Kainic Acid / toxicity
  • Mice
  • Mice, Inbred DBA
  • Noise / adverse effects
  • Receptors, GABA / physiology
  • Receptors, Interleukin-2 / physiology
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / toxicity

Substances

  • Convulsants
  • Interleukin-2
  • Receptors, GABA
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Cefazolin
  • Kainic Acid
  • Bicuculline