Antidepressant treatment of cytokine-induced mood disorders

Significant evidence suggests that the immune system is capable of profoundly affecting central nervous system (CNS) functioning in ways that may contribute to the development and expression of neuropsychiatric disorders, including disorders of mood. This paper reviews evidence that the production of proinflammatory cytokines, whether in the context of therapeutic administration (e.g. interferon-α-2b for hepatitis C infection) or medical illness, induces a state of sickness behavior that closely resembles major depression. Antidepressants have been shown to abolish or attenuate cytokine-induced sickness behavior in laboratory animals and to protect against the development of major depression in the context of therapeutic cytokine administration in humans. Potential mechanisms by which antidepressants ameliorate depressive and/or sickness symptoms in the context of immune activation include direct effects on immune cell functioning, as well as modulatory effects on monoamine neurotransmitters, intracellular second messenger pathways and the neuroendocrine system, in particular the hypothalamic-pituitary-adrenal axis.