title: The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression.
abstract: Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression. Hippocampal glucocorticoid receptors (GRs) and the associated hypothalamus-pituitary-adrenal (HPA) axis have close interactions with pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the anti-oxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GRs have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation.
authors.affiliation: Department of Psychiatry, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong-Ku
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Gachon University Gil Medical Center, Incheon, Republic of Korea. Electronic address: ksna13@gmail.com.
authors.forename: Kyoung-Sae
authors.initials: KS
authors.lastname: Na
authors.affiliation: Laboratory for Psychoneuroimmunology, Psychiatric Hospital, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Aye-Mu
authors.initials: AM
authors.lastname: Myint
authors.affiliation: Pharmacology Department, National University of Ireland, Galway, Ireland; Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Leonard
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000503:physiopathology*; D006801:Humans; D055495:Neurogenesis / Q000502:physiology*; D015213:Neuroimmunomodulation / Q000502:physiology*; D009490:Neurosecretory Systems / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D016207:Cytokines
keywords: Antioxidants; Cytokine; Depression; Glucocorticoid receptor; Neuroinflammation; Oxidative stress