Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures
Section snippets
Experiments
IL-6 null knock-out (KO) mice36 were kindly provided by Dr Horst Bluethmann (CNS Department, Pharma Research Gene Technologies, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland).
In a first experiment, adult normal (1295 v, n=8) and IL-6 KO (n=8) mice were injected i.p. with 35 mg/kg KA, which is a glutamate receptor agonist with excitotoxic effects.40 The number of mice showing seizures as well as the mortality were recorded. Because of the high mortality of the IL-6 KO mice, no
Susceptibility to kainic acid
Saline-injected mice of normal and IL-6 KO genotypes showed similar behavioral patterns. No spontaneous convulsions were seen in these mice. The administration of 35 mg/kg KA produced convulsions in both normal and IL-6 KO mice (Table 1), but the percentage of mice seizing and the number of convulsions were higher in the latter (P<0.05). Moreover, five out of eight (62.5%) of the IL-6 KO mice died in the following few hours after the KA administration, while none of the control mice died (P
Discussion
The IL-6 null mice are a unique tool for analysing the role of this cytokine on KA-induced hippocampal damage. The results clearly show that the IL-6 mice are more susceptible to KA-induced seizures, with a higher percentage of animals seizing and a greater mortality compared to control mice. Associated with this increased susceptibility, the IL-6 mice showed an impaired glial response to KA-induced seizures, an unbalanced antioxidant profile that led to an increased oxidative stress, and an
Conclusions
The present report demonstrates that IL-6 deficiency impairs significantly the gliosis induced by KA-induced seizures, and increases the oxidative stress and the neuronal death, processes where the partially blunted MT-I+II expression may have a relevant role.
Acknowledgements
We are indebted to Dr Horst Bluethmann (CNS Department, Pharma Research Gene Technologies, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland) for his continuous support and for the generous gift of the IL-6 KO mice. The superb excellent technical assistence of Hanne Hadberg, Pernille S. Thomsen, Mette Søberg, Grazyna Hahn, Birgit Risto and Keld Stub is gratefully acknowledged. These studies were supported by Hjerteforeningen (MP), Kong Christian X's Fond (MP), Boldings Fond (MP), Fonden til
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