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-1beta 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-1beta 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-1beta concentrations in the hippocampus.


RESULTS
We report that interleukin-1beta increased lipid peroxidation in hippocampal tissue prepared from 4- but not 22-month-old rats, and that this effect was inhibited by alpha-tocopherol. The attenuated response to interleukin-1beta in tissue prepared from aged rats correlated with increased expression of endogenous interleukin-1beta. Thus, using an ELISA, we have demonstrated an age-related increase in the concentration of interleukin-1beta, which is accompanied by an age-related decrease in membrane arachidonic acid.


CONCLUSIONS
We propose that increased interleukin-1beta expression impacts on membrane composition and therefore contributes to age-related impairments in neuronal function.
Murray
C A
CA
Department of Physiology, Trinity College, Dublin, Ireland, UK.
Clements
M P
MP
Lynch
M A
MA
D000375:Aging / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017382:Reactive Oxygen Species; D012795:Sialoglycoproteins; D014810:Vitamin E; D016718:Arachidonic Acid