Increased IL-1β in cortex of aged rats is accompanied by downregulation of ERK and PI-3 kinase

Ageing is accompanied by a myriad of changes, which lead to deficits in synaptic function and recent studies have identified an increase in concentration of the proinflammatory cytokine, interleukin-1beta (IL-1beta), as a factor which significantly contributes to deterioration of cell function. Here, we consider that increased IL-1beta concentration and upregulation of IL-1beta-induced cell signalling cascades may be accompanied by downregulation of survival signals, perhaps as a consequence of decreased neurotrophins-associated signalling. The data indicate that increased IL-1beta concentration was coupled with downregulation of ERK and phosphoinositide-3 kinase (PI-3 kinase) in cortical tissue prepared from aged rats. These changes could not be attributed to decreased concentration of NGF or BDNF but the evidence suggested that they may be a consequence of an age-related change in the anti-inflammatory cytokine, IL-4. Significantly, treatment of aged rats with eicosapentaenoic acid reversed the age-related increases in IL-1beta and IL-1beta-induced signalling and also the age-related changes in IL-4, ERK and PI-3 kinase. (C) 2003 Elsevier Inc. All rights reserved.