Effects of interleukin-2 on various models of experimental epilepsy in DBA/2 mice.
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)
De Sarro
G
G
Department of Experimental and Clinical Medicine, Faculty of Medicine, University of Reggio Calabria, Catanzaro.
Rotiroti
D
D
Audino
M G
MG
Gratteri
S
S
Nisticó
G
G
D000818:Animals; D001640:Bicuculline / Q000633:toxicity; D002437:Cefazolin / Q000633:toxicity; D003292:Convulsants / Q000494:pharmacology / Q000633:toxicity*; D004569:Electroencephalography / Q000187:drug effects; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D007276:Injections, Intraventricular; D007376:Interleukin-2 / Q000494:pharmacology / Q000633:toxicity*; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008811:Mice, Inbred DBA; D009622:Noise / Q000009:adverse effects; D018079:Receptors, GABA / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology / Q000633:toxicity
D003292:Convulsants; D007376:Interleukin-2; D018079:Receptors, GABA; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D002437:Cefazolin; D007608:Kainic Acid; D001640:Bicuculline