Clinical and experimental studies on animals indicate that depression is associated with increased plasma cytokine acute phase protein concentrations and hypothalamic-pituitary-adrenal axis (HPA) activation. Additionally it has been detected that immunological activation induces stress-like behavioural and neurochemical changes in organisms of animals and humans. Hypersecretion of cytokines in response to stress or to endogenous trigger factors may induce depressive symptoms. Corticotropin releasing hormone (CRH) overproduction in the brain also may participate in cytokine-induced behavioural and neurochemical changes. Treatment with antidepressants conferred protection against cytokine-induced depressive-like biological and behavioural changes. This is mainly due to alterations of the pro-/anti-inflammatory cytokine balance. There is a substantial body of evidence that the immune system plays a major role in aetiology of depression and that cytokines participate in neurochemical, behavioural and endocrine changes in this illness.