Protective effect of IL-18 on kainate- and IL-1 beta-induced cerebellar ataxia in mice.
The pathogenesis of sporadic cerebellar ataxia remains unknown. In this study, we demonstrate that proinflammatory cytokines, IL-18 and IL-1beta, reciprocally regulate kainate-induced cerebellar ataxia in mice. We show that systemic administration of kainate activated IL-1beta and IL-18 predominantly in the cerebellum of mice, which was accompanied with ataxia. Mice deficient in caspase-1, IL-1R type I, or MyD88 were resistant to kainate-induced ataxia, while IL-18- or IL-18R alpha-deficient mice displayed significant delay of recovery from ataxia. A direct intracerebellar injection of IL-1beta-induced ataxia and intracerebellar coinjection of IL-18 counteracted the effect of IL-1beta. Our data firstly show that IL-18 and IL-1beta display differential direct regulation in kainate-induced ataxia in mice. Our results might contribute toward the development of a new therapeutic strategy for cerebellar ataxia in humans.
Andoh
Tsugunobu
T
Department of Applied Pharmacology, Uniuversity of Toyama, 2630 Sugitani, Toyama, Japan.
Kishi
Hiroyuki
H
Motoki
Kazumi
K
Nakanishi
Kenji
K
Kuraishi
Yasushi
Y
Muraguchi
Atsushi
A
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D020170:Caspase 1 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D002524:Cerebellar Ataxia / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D020382:Interleukin-18 / Q000502:physiology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D007608:Kainic Acid / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D020382:Interleukin-18; D053583:Interleukin-1beta; D020170:Caspase 1; D007608:Kainic Acid