Changes in the immune system in depression and dementia: causal or co-incidental effects?

It is now widely accepted that psychological stress and psychiatric illness can compromise immune function. Furthermore the mechanisms whereby such ch anges occur are probably associated with the activities of the cytokines an d other inflammatory mediators of the immune system which are known to init iate changes in behaviour, This review aims to summarise the experimental a nd clinical evidence that implicates the pro-inflammatory cytokines in the pathological changes seen in major depression and in Alzheimers disease (AD ). In major depression, evidence is provided to show that both activation ( e.g.. macrophage activity, acute phase proteins) and inhibition (e.g., natu ral killer cell activity) of the immune system occur. Many of the behaviour al changes seen in depression are simulated by three pro-inflammatory cytok ines (IL-1, IL-6 and TNF-alpha). which may produce their impact on the brai n by activating cyclooxygenase, nitric acid synthase and corticotrophin rel easing factor. Effective antidepressant treatments largely attenuate the im mune changes thereby raising the possibility that the normalisation of cent ral biogenic amine function that are conventionally implicated in the cause of depression may be secondary to those of the pro-inflammatory cytokines. With respect to AD, while the cause(s) are unknown, there is both experimen tal and clinical evidence to suggest that inflammatory processes in the bra in caused in particular by TNF-alpha together with the subsequent rise in f ree radicals, are instrumental in causing the pathological changes which un derlie the disease. Evidence in favour of the inflammatory hypothesis is su pported by the finding that nonsteroidal anti-inflammatory drugs slow down the progression of the disease. Although, more research is needed into the inter-relationships between the various pro-inflammatory cytokines and the behavioural changes invoked in m ajor depression and AD, the immunological hypothesis has been important in stimulating new concepts regarding the causes of the pathological changes i n these diseases and how effective drug treatments may attenuate them. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.