Depression, cytokines, and glial function

It has been known for some time that cytokines made and released during systemic illness can result in a constellation of symptoms strikingly similar to those observed in depression. The overlap of the symptoms of depression and systemic illness raises the intriguing possibility that cytokines may be involved in the development and maintenance of mood disorders. Cytokines are small ubiquitous pleiotropic molecules that are made and released in response to a variety of stimuli. They have a multitude of actions throughout the body, including actions on the central and peripheral nervous systems. Alterations in the levels of circulating cytokines, especially the key proinflammatory cytokines, interleukin 6 and tumor necrosis factor α, have been linked to a variety of disease states including those involving central nervous system depression. In this brief review, epidemiological and clinical data on depression, as well as findings from relevant animal models, are examined for links between cytokine expression and depression. We suggest that glial cells, both as a source and target of cytokines, represent the overlooked targets involved in the etiology of depression.