From inflammation to sickness and depression: when the immune system subjugates the brain

Cytokines, produced in response to peripheral infections, act in the brain to cause sickness behaviour. Dantzer and colleagues consider the intriguing hypothesis that prolonged immune signalling in the brain can cause symptoms of depression and discuss the mechanisms that might underlie this phenomenon. In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.