Inflammation, Serotonin and Major Depression

Catena-Dell’Osso, Mario; Rotella, Francesco; Dell’Osso, Adriana; Fagiolini, Andrea; Marazziti, Donatella

doi:10.2174/13894501113149990154

Cited by 92 publications

(62 citation statements)

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“…According to the cytokine hypothesis, depressive disorders are related to increased production of cytokines, including interleukins, tumor necrosis factor alfa (TNF-α), and interferon-α and -γ. 1 A meta-analysis of cytokines in major depression shows higher concentrations of pro-inflammatory cytokines IL-6 and TNF-α in depressed patients compared with control subjects. 2 Fluoxetine is an antidepressant from the group of selective serotonin reuptake inhibitors (SSRI).…”

Section: Introductionmentioning

confidence: 99%

Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

et al. 2015

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The aim of the present study was to evaluate the anti-inflammatory effect of fluoxetine in carrageenan-and lipoplysaccharideinduced models of inflammation by investigating the changes in serum levels of pro-inflammatory cytokine TNF-α and anti-inflammatory cytokines IL-10 and TGF-β after single and repeated administration of the drug. To study the effect of a single and repeated dose fluoxetine on carrageenan-induced paw edema male Wistar rats were divided into five groups (n = 8): control group; positive control group; and three experimental groups treated with 5, 10, and 20 mg/kg bodyweight (bw) fluoxetine, respectively. To study the effect of a single and repeated dose of fluoxetine on serum cytokine levels, the animals were divided in four groups (n = 8): two control groups treated with saline and two experimental groups treated with fluoxetine 20 mg/kg bw. Carrageenan and LPS were injected immediately after fluoxetine or saline injection. Serum cytokine concentrations were tested by enzyme immunoassay. In single administration only the highest dose used inhibited carrageenan-induced inflammation. Edema inhibition was seen with 10 and 20 mg/kg bw fluoxetine after repeated administration. At 24 h a statistically significant effect on inhibition of carrageenan edema was found only in rats treated with 20 mg/kg bw fluoxetine In carrageenan-induced inflammation, fluoxetine significantly increased Il-10 and decreased TNF-α after repeated administration. Surprisingly, in single-dose treated animals an increase in TNF-α values upon fluoxetine administration was observed in this model of inflammation. In LPS-induced inflammation, fluoxetine significantly decreased TNF-α after single and repeated treatment. Fluoxetine has anti-inflammatory and immunomodulatory effect in the carrageenan-induced model of exudative inflammation. In LPS-induced inflammation it showed an immunomodulatory effect manifested with a decrease in pro-inflammatory cytokine TNF-α.

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Section: Introductionmentioning

confidence: 99%

Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

et al. 2015

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“…This implies a strong competition between serotonin and the first downstream metabolites from the kynurenine pathway, kynurenine, for the available tryptophan, as described below. In inflammatory conditions, more kynurenine is produced on the expenses of serotonin [43,44], which, if happens also in the brain, results in behavioral changes including persistent sadness, loss of interest, and decreased energy levels [45] (Figure 1A). …”

Section: Gastrointestinal Inflammation and Depressionmentioning

confidence: 99%

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

Waclawiková¹,

Aidy²

2018

Preprint

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The human gastrointestinal tract is inhabited by trillions of commensal bacteria collectively known as the gut microbiota. Our recognition of the significance of the complex interaction between the microbiota, and its host has grown dramatically over the past years. A balanced microbial community is a key regulator of the immune response, and metabolism of dietary components, which in turn, modulates several brain processes impacting mood and behavior. Consequently, it is likely that disruptions within the composition of the microbiota would remotely affect the mental state of the host. Here, we discuss how intestinal bacteria and their metabolites can orchestrate gut-associated neuroimmune mechanisms that influence mood and behavior leading to depression. In particular, we focus on microbiota-triggered gut inflammation and its implications in shifting the tryptophan metabolism towards kynurenine biosynthesis while disrupting the serotonergic signaling. We further investigate the gaps to be bridged in this exciting field of research in order to clarify our understanding of the multifaceted crosstalk in the microbiota-gut-brain interphase, bringing about a novel microbiota-targeted therapeutics for mental illnesses.

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“…Depression could be due to a stress-related increase in the production of cytokines such as ILs, TNF-α, IFN-α, IFN-β, and IFN-γ, which, in turn, up-regulate indoleamine 2,3-dioxygenase (IDO) expression [62][63][64][65] . IDO converts tryptophan, the precursor of 5-HT, to kynurenine; so IDO activation leads to reduced levels of tryptophan and thus reduced central 5-HT synthesis [66][67][68] .…”

Section: -Hydroxytryptamine Pro-inflammatory Cytokines Havementioning

confidence: 99%

Inflammation: a mechanism of depression?

Han

2014

Neurosci. Bull.

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In recent decades, major depression has become more prevalent and research has shown that immune activation and cytokine production may be involved. This review is mainly focused on the contribution of infl ammation to depression. We fi rst briefl y introduce the infl ammatory biomarkers of depression, then discuss the sources of cytokines in the brain, and fi nally describe the neuroimmunological mechanisms underlying the association between infl ammation and depression.Keywords: depression; infl ammation; cytokines; hypothalamic-pituitary-adrenal axis; 5-HT; neuroplasticity ·Review· IntroductionThe prevalence of major depression has increased dramatically over the past few decades [1] , and women are nearly twice as likely as men to develop depressive disorder [2] . Depression is classified as a brain disorder, but its symptomatology includes some behaviors that also occur during chronic infl ammatory stress [3] . Research has shown that immune activation and the production of cytokines may be involved in depression [4] , so this relationship has received much attention. In fact, three causal pathways have been proposed: depression to inflammation, inflammation to depression, and a bidirectional relationship [5] . In this review, we focus on the impact of inflammation on depression and the underlying mechanisms. Cytokines are small cell-signaling proteins that mediate and regulate immune responses and inflammation, and can be divided into two categories:the pro-inflammatory cytokines interleukin (IL)-1 β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokines IL-1Rα, IL-4, IL-10, and transforming growth factor (TGF)-β1. Generally, t he proinfl ammatory cytokines promote systemic infl ammation and are essential for the initiation of an infl ammatory response to disease [6] , while the anti-inflammatory cytokines antagonize these actions to reduce inflammation and promote healing [6,7] . Moreover, some cytokines play dual roles [8] . In the central nervous system (CNS), the cellular source, function, and mechanisms of action of cytokines differ from those in the periphery. In the following, we briefl y introduce the current research on infl ammatory biomarkers of depression. Infl ammatory Biomarkers of DepressionSo far, there are neither universally accepted or defi nitive biomarkers of depression [9] , nor effective methods to assess the severity, endophenotypes, or response to treatment [10] .However, sufficient evidence has suggested changes in the circulating levels of cytokines in depressed patients, which can be reversed by antidepressant treatments [11,12] .So, many studies have aimed to clarify the neurobiological changes in depression and to establish inflammatory biomarkers. The peripheral levels of IL-6, TNF-α, and IL-1β are increased in patients with depression [13][14][15][16][17] , and antidepressant treatments reverse this effect [18][19][20] . These consistent results demonstrate that IL-6, TNF-α, and IL-1β are putative biomarkers for depression. However, due to the he...

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Inflammation, Serotonin and Major Depression

Cited by 92 publications

References 0 publications

Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression

Inflammation: a mechanism of depression?

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