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)

Behavioural and ECoG spectrum changes induced by intracerebral infusion of interferons and interleukin 2 in rats are antagonized by naloxone.

Rat interferon, alpha-interferon, interleukin 2 and recombinant interleukin-2 injected into the third cerebral ventricle produced typical behavioural sedation and/or sleep and ECoG synchronization in rats while beta-interferon produced no behavioural sleep or ECoG synchronization. A slight sedation was observed after the largest dose of beta-interferon only. During sleep induced by lymphokines, a dose-dependent increase in total voltage power as well as in the 0.5-3, 4-7 and 12-16 Hz frequent bands was observed. Much smaller doses were required to produce similar behavioural and ECoG spectrum effects after infusion of interferons and interleukin-2 into the locus coeruleus. No significant behavioural and ECoG changes were obtained after infusion of the same doses of interferons and interleukin-2 into other areas of the brain (caudate nucleus, dorsal hippocampus, substantia nigra pars compacta, ventromedial hypothalamus). The behavioural and ECoG effects of alpha-interferon, rat interferon and interleukin-2 were blocked in animals pretreated with naloxone. These results are consistent with the hypothesis that the behavioural and ECoG effects of these lymphokines are mediated at locus coeruleus level by stimulation of opiate receptors.

Behavioural and electrocortical effects after injection of two ornithine decarboxylase inhibitors into several areas of the brain in the rat.

The behavioural and electrocortical effects of alpha-methylornithine and alpha-difluoromethylornithine, two ornithine decarboxylase inhibitors, were evaluated after their infusion into several areas of the brain in the rat. Both compounds induced, in dose-dependent manner, similar epileptogenic effects, stereotyped behaviour and postural asymmetry, depending upon the site of injection. Unilateral injection of DFMO into the entopeduncular nucleus or the substantia nigra pars reticulata, caused an increase in locomotor activity. Unilateral injection of DFMO into the caudate nucleus or the substantia nigra pars compacta had no effect on locomotor activity. Among the areas of the brain studied, the most sensitive site from which electrocortical epileptogenic disorders were evoked, was the hippocampus. The GABA agonist muscimol, infused prior to DFMO, resulted in an anticonvulsant action, while DFMO, infused prior to putrescine, increased the convulsant properties of putrescine. In conclusion, these results indicate that DFMO and alpha-methylornithine produced epileptogenic effects after their intracerebral infusion and suggest that may act as analogues of putrescine.