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.

The Role of Immune System in Depression Disorder

“…Based on the current research, cytokines and GRs, as the important factors in inflammatory and endocrine processes, have a major role in the depression [5].…”

“…[4]. They also have an important role in immune responses, neurogenesis and neuroprotection which are mediated by macrophages and monocytes [5].…”

Effect and Disease Indicative Role of Inflammation in Neurodegenerative Pathology: A Mechanistic Crosstalk of Promise and Dilemma

“…An acute neuroinflammatory response is therefore considered helpful in reducing risk of damage as it activates our innate immunity. Conversely, chronic inflammation involves standby activation of microglia preventing release of inflammatory mediators causing increase oxidative stress together with nitrosative stress endless extending the inflammation cycle, which adversely affects neurodegenerative diseases [111][112][113]. It has been reported that, T-cells infiltrate CNS and regulate the functions of neurons and glial cell population.…”

Neuroinflammation and Mitochondrial Dysfunction in the Pathogenesis of Alzheimer?s Disease: Modulation by Coriolus Versicolor (Yun-Zhi) Nutritional Mushroom

“…Recent studies have demonstrated that the inflammasome modulates neuroinflammatory processes at the initial stage, with a secondary cascade of events inclusive of oxidative stress, having been shown to possess the ability to activate the inflammasome 60 . The inflammasome is a macromolecular complex that contains multiple copies of a receptor for pathogen-or damagederived molecular patterns (PAMPs, pro-caspase-1, and an adaptor, apoptotic speck-containing protein with a CARD [ASC], which induces caspase-1 maturation 61 .…”