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OBJECTIVE: This article reviews recent developments in cytokine biology that are relevant to clinical psychiatry.METHOD: The authors reviewed English-language literature of the last 15 years that pertains to the biology of cytokines with emphasis on central nervous system effects in general and psychiatric disorders in particular.RESULTS: Growing evidence suggests that, in addition to providing communication between immune cells, specific cytokines play a role in signaling the brain to produce neurochemical, neuroendocrine, neuroimmune, and behavioral changes. This signaling may be part of a generalized, comprehensive mechanism to mobilize resources in the face of physical and/or psychological stress and to maintain homeostasis. The clinical implications of these findings are far-reaching and include a possible role for cytokines in the pathophysiology of specific psychiatric disorders such as major depression, schizophrenia, and Alzheimer’s disease. The effects of cytokines in the central nervous system may provide a possible mechanism for the “sickness behavior” of patients with severe infection or cancer, as well as for the neuropsychiatric adverse effects of treatment with interferons and interleukins.CONCLUSIONS: A better understanding of the role of cytokines in various brain activities will enhance knowledge of specific psychobiological mechanisms in health and disease and provide opportunities for novel treatment interventions.