Cytokines, stress, and depressive illness.

It has been suggested that immune activation, and particularly increased activity of several cytokines, notably interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-alpha as well as their soluble receptors is characteristic of depression. Normalization of cytokine activity does not necessarily occur following successful antidepressant, suggesting that cytokines may be trait markers of depression, or simply represent bystander effects of the illness. The relationship between cytokines and depression is complicated as a variety factors could directly or indirectly influence cytokine activity. While cytokine elevations are most pronounced in severe (melancholic) depression, their activity may also be related to chronicity of illness, neurovegetative features of depression (altered sleep patterns, food intake, weight changes, fatigue or general activity), or the high stress perception characteristic of depression. Although, studies assessing cytokines in depressive populations are basically correlational in nature, patients receiving cytokine immunotherapy frequently show depressive symptoms, which may be attenuated by antidepressant medication, supporting a causal role for cytokines in depressive disorders. The processes underlying such outcomes remain to be established, but the affective changes may stem from the neuroendocrine and central neurochemical changes elicited by cytokines, as these are reminiscent of those associated thought to subserve depression.