Interleukin-1 induces lipid peroxidation and membrane changes in rat hippocampus: An age-related study

Background: The proinflammatory cytokine, interleukin-1, is traditionally associated with the immune response but recent evidence indicates that it plays a role in neuronal function. Its expression is increased in neurodegenerative conditions and preliminary evidence suggests that it is also increased with increasing age. Receptors for interleukin-1 are differentially distributed in the brain with a high density in the hippocampus, where interleukin-1 beta exerts inhibitory effects on release and calcium channel function, Objective: The aim of this study was to investigate the possibility that interleukin-1 might lead to age-related changes in membrane composition. Methods: Lipid peroxidation was assessed in the presence or absence of interleukin-1 beta in hippocampal tissue prepared from 4- and 22-month-old rats, These data were analysed in parallel with age-related changes in arachidonic acid and interleukin-1 beta concentrations in the hippocampus. Results: We report that interleukin-1 beta increased lipid peroxidation in hippocampal tissue prepared from 4- but not 22-month-old rats, and that this effect was inhibited by a-tocopherol. The attenuated response to interleukin-1 beta in tissue prepared from aged rats correlated with increased expression of endogenous interleukin-1 beta. Thus, using an ELISA, we have demonstrated an age-related increase in the concentration of interleukin-1 beta, which is accompanied by an age-related decrease in membrane arachidonic acid, Conclusion: We propose that increased interleukin-1 beta expression impacts on membrane composition and therefore contributes to age-related impairments in neuronal function.