Effects of antidepressants on cytokine production and actions.
There are intriguing analogies between many features of depression and physiological and behavioral responses to infection, which are mediated by the brain effects of cytokines. These observations suggest that depression can be considered as a psychoneuroimmunological disorder where a central increase of pro-inflammatory cytokines, may have adverse consequences on the functional activity of the neurochemical and neuroendocrine systems implicated in the symptoms of the disorder. According to this hypothesis, the therapeutic effects of antidepressants should be at least partly exerted by attenuating the brain expression and/or actions of pro-inflammatory cytokines. Despite their inherent limitations, animal models of depression that are based on behavioral and pharmacological analogies with the symptoms observed in humans, represent the best available tool to test this hypothesis and to investigate the action mechanisms of the immune effects of antidepressants. Treatment with different classes of antidepressants indeed conferred protection against cytokine-induced depressive-like biological and behavioral changes. This 'anti-inflammatory' profile may be due to alterations of the pro-/anti-inflammatory cytokine balance. The mechanisms underlying these effects of antidepressants are presently unknown, but the available literature suggests several possibilities, including actions on different molecules representing potential mediators of mood disorders induced by cytokines. The studies summarized in this review have opened up new vistas in both the pathophysiology of depression and the pharmacology of antidepressants. Whether their demonstrated immune effects are a side effect or a significant part of their clinical activity still remains to be elucidated.
Castanon
Nathalie
N
INRA-INSERM U394, Neurobiologie Integrative, Institut François Magendie, Rue Camille Saint-Saëns, Bordeaux Cedex 33077, France. nathalie.castanon@bordeaux.inserm.fr
Leonard
Brian E
BE
Neveu
Pierre J
PJ
Yirmiya
Raz
R
D000818:Animals; D000928:Antidepressive Agents / Q000276:immunology* / Q000494:pharmacology*; D016207:Cytokines / Q000009:adverse effects* / Q000187:drug effects*; D003863:Depression / Q000276:immunology; D003866:Depressive Disorder / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D013315:Stress, Psychological / Q000276:immunology
D000928:Antidepressive Agents; D016207:Cytokines