Cytokine-induced sickness behavior and depression

Sickness behavior refers to a set of non-specific responses that develop in humans and animals during the course of an infection. Sickness symptoms possess motivational features and evolutionary values that favor survival of organisms during infection. The discovery that proinflammatory cytokines induce sickness behaviors forms a cornerstone for elucidating immune-to-brain communication systems. Cytokines produced in the periphery by leukocytes during infection and chronic inflammatory diseases serve as messengers that are sent to the brain via neural and humoral routes to activate a diffuse cytokine system that mirrors that in the periphery. The brain initiates a series of events that induce behavioral changes collectively known as sickness behaviors. Sickness behavior is now recognized to be part of a highly-organized host response to infection. However, prolonged activation of the innate immune system, as occurs during chronic infectious diseases and non-infectious diseases with inflammatory components, can lead to symptoms of depression in vulnerable individuals. Recent clinical findings have implicated the tryptophan-degrading enzyme, indoleamine 2, 3 dioxygenase (IDO), as a potential mediator of inflammation-Associated depression. Experimental data obtained in animal studies have provided molecular support for such a relationship. Here we discuss the current evidence that favors the view that acute inflammation induces sickness behavior whereas chronic inflammation can lead to depressive-like behaviors that are mediated by IDO.