Cytokines and depression

Abstract

Publisher Summary Mood can be modulated by inflammatory cytokines, corticotropin-releasing factor (CRF), and cortisol. In parallel, inflammatory cytokines can modulate neuroendocrine function and vice versa. Under normal circumstances, the homeostatic regulation of the interaction among these factors is finely tuned and adaptive for survival. However, when one system becomes dysregulated the others are affected. Major depression is characterized by reduced natural killer (NK) cell activity, increased production of T helper-1 (Th1) and pro-inflammatory cytokines, and stimulation of the acute-phase response as well as increased CRF and cortisol. The origin of this physiologically maladaptive milieu may be either prolonged inflammatory illness (or immune dysregulation that mimics inflammatory illness) or chronic uncontrollable stress. This is possible as both pro-inflammatory cytokines and psychological stress activate the hypothalamic–pituitary–adrenal (HPA) axis response system. Repeated activation of this system, by either route, induces desensitization of the regulatory negative feedback receptors in the brain, pituitary gland, and lymphocytes. Once the capacity for regulation is lost, the elevated levels of inflammatory cytokines, CRF, and cortisol can prevail, all of which can have a negative influence on mood.