The increase in plasma concentrations of the pro-inflammatory cytokines observed in patients suffering from depression is known to be closely correlated with the severity of this psychiatric disorder, the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and the deficiency in serotonergic (5-HT) neurotransmission. Several medical conditions e.g. autoimmune disease such as rheumatoid arthritis (RA), cancer or hepatitis C therapies producing activation of the immune system are associated with psychological and neuroendocrine changes that resemble the characteristics of depression including depressed mood, appetite disturbance, sleep disturbance, psycho motor disturbance, fatigue, loss of energy, difficulty in thinking or concentrating, activation of the immune system, hyperactivity of HPA axis and monoaminergic alterations. Similarly, administration of pro-inflammatory cytokines in animals induces 'sickness behavior' which is a pattern of behavioral symptoms that are very similar to those of depression in humans. Furthermore, treatment of antidepressants in depression attenuates cytokine production and their action. Cytokine therapy itself alleviates symptoms of depression in medical conditions and animal experiments. These results indicate that activation of the immune system is associated with behavioral, neuroendocrine and neurochemical changes that resemble the characteristics of depression and suggest that pro-inflammatory cytokines are involved in the aetiology and pathophysiology of depression. In the present review, the current knowledge on the possible role of pro-inflammatory cytokines such as IL-1, TNF-Ձ and IFN-Ճ in depression is discussed.

Keywords: depression, pro-inflammatory cytokines, IL-1, TNF-Ձ,, IFN-Ճ,