Abstract: In the research field of psycholoneuroimmunology, accumulating evidence has indicated the existence of reciprocal communication pathway between nervous and immune system. “The cytokine hypothesis of depression” implies that proinflammatory cytokines, acting as neuromudulators, represent the key factor in the central mediation of the behavioral, neuroendocrine and neurochemical features of depression. This view is supported by various findings. Administration of proinflammatory cytokine in animal induces “sickness behavior”, which is very similar to the behavioral symptoms of depression in humans. Cytokines produced by peripheral immune activity, which could signal to the brain via a fast neural pathway and a slower humoral pathway, together with the cytokines produced within central nervous system exert central effects. Cytokines may cause hypothalamic-pituitary adrenal axis hyperactivity by disturbing the negative feedback inhibition of circulating corticosteroids on the hypothalamic-pituitary adrenal axis. Otherwise, cytokines may reduce 5-hydroxytryptamin level by lowering the availability of its precursor tryptophan through activation of the trypyophan-metabolising enzyme indoleamine-2, 3-dioxygenase.The central effects of cytokines appear to be able to account for most of the symptoms occurring in depression, and “cytokine hypothesis of depression” has created new perspectives in the mechanism study and the therapy of depressive symptoms

Key words: depression, cytokine, hypothalamic-pituitary-adrenal axis, 5-hydroxytryptamin, sickness behavior