On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?

Abstract

Many patients with major depressive disorder (MDD) are reported to have higher levels of multiple inflammatory cytokines including interleukin 6 (IL-6). Recent studies both pre-clinical and clinical have advocated for the functional role of IL-6 in development of MDD and suggested a great potential for targeting this cytokine to open new avenues in pharmacotherapy of depression. The purpose of the present narrative review was to provide an integrated account of how IL-6 may contribute to development of depression. All peer-reviewed journal articles published before July 2020 for each area discussed were searched by WOS, PubMed, MEDLINE, Scopus, Google Scholar, for original research, review articles, and book chapters. Publications between 1980 and July 2020 were included. Alterations in IL-6 levels, both within the periphery and the brain, most probably contribute to depression symptomatology in numerous ways. As IL-6 acts on multiple differing target tissues throughout the body, dysregulation of this particular cytokine can precipitate a multitude of events relevant to depression and blocking its effects can prevent further escalation of inflammatory responses, and potentially pave the way for opening new avenues in diagnosis, treatment, and prevention of this debilitating disorder.

The Feasibility of Tai Chi Exercise as a Beneficial Mind-Body Intervention in a Group of Community-Dwelling Stroke Survivors with Symptoms of Depression

“…Moreover, IL-6 levels correlate differently among different depression subtypes, symptomology, and may be confounded by chronic inflammatory conditions that are often comorbid with ischemic stroke. Complicating our interpretation of IL-6 biomarker data further, prior research indicates that IL-6 exerts both pro- and anti-inflammatory properties [ 73 , 74 ]. While IL-6 is generally regarded as having proinflammatory properties, research indicates it has many anti-inflammatory functions as well.…”

Prognostic value of long-term trajectories of depression for incident diabetes mellitus in patients with stable coronary heart disease

“…DM is associated with chronic low-grade inflammation [ 24 ], as is depression [ 25 – 28 ]. Also, anti-cytokine treatments exhibit antidepressant effects in chronic inflammatory conditions [ 29 ], pointing to a causal role of chronic inflammation in the etiology of depression.…”

Skin-brain axis signaling mediates behavioral changes after skin wounding

“…( Johnson et al., 2020 ), ( Bosurgi et al., 2017 ; Braune et al., 2017 ), ( Wood et al., 2011 ) Given our findings that serum IL6 was increased at 6 days post-wounding, this would suggest it is involved in regulating wound resolution. There is also extensive documentation of strong correlation of elevated IL6 serum levels in patients with major depressive disorder ( Hadian et al., 2020 ; Roohi et al., 2021 ). While the exact underpinnings of this association are not completely understood, one documented action of IL6 is the control of the level of the serotonin transporter, and subsequently serotonin uptake ( Kong et al., 2015 ).…”

“…Monoamines, especially dopamine, are essential for memory formation ( Wise, 2004 ) and altered CNS dopamine signaling has been associated with cognitive dysfunction in a number of diseases ( Calabresi et al., 2006 ; Braver and Cohen, 1999 ; Pan et al., 2019 ). Additionally, systemic levels of inflammatory cytokines have also been associated with cognitive deficits in patients with post-traumatic stress disorder, and major depressive disease ( Hadian et al., 2020 ; Imai et al., 2018 ; Roohi et al., 2021 ). We hypothesized that the affective and cognitive symptoms in subjects with chronic skin wounds associate with alterations in CNS monamines, or with systemic elevation of inflammatory cytokines, and sought to determine the signaling pathways between peripheral wounds and the central nervous system.…”