Antidepressant effects of TNF-α blockade in an animal model of depression

Krügel, Ute; Fischer, Johannes; Radicke, Susanne; Sack, Ulrich; Himmerich, Hubertus

doi:10.1016/j.jpsychires.2013.01.007

Cited by 94 publications

(48 citation statements)

References 51 publications

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“…Moreover, blockers of these cytokines, for example the TNF-a blocker etanercept, demonstrate antidepressant effects in animals (Krügel et al 2013) and humans (Tyring et al 2006). The fact that lithium treatment of depressed patients increases pro-inflammatory cytokine plasma levels (Himmerich et al 2005) and activates pro-inflammatory cytokine production in vitro questions the general applicability of these cytokines as biomarkers for depression, because lithium augmentation has a reliable antidepressant effect even in therapy resistant depressed patients (Bschor et al 2003) despite its activating effect on cytokine production.…”

Section: Discussionmentioning

confidence: 99%

Impact of lithium alone and in combination with antidepressants on cytokine production in vitro

et al. 2014

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Lithium is an important psychopharmacological agent for the treatment of unipolar as well as bipolar affective disorders. Lithium has a number of side effects such as hypothyroidism and aggravation of psoriasis. On the other hand, lithium has pro-inflammatory effects, which appear beneficial in some disorders associated with immunological deficits, such as human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE). Therefore, immunological characteristics of lithium may be an important consideration in individualized therapeutic decisions. We measured the levels of the cytokines interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-22, IL-17 and tumour necrosis factor (TNF)-α in the stimulated blood of thirty healthy subjects supplemented with lithium alone, the antidepressants citalopram, escitalopram or mirtazapine alone, the combination of each antidepressant with lithium, and a no drug control. These drugs were tested under three blood stimulant conditions: murine anti-human CD3 monoclonal antibody OKT3 and the 5C3 monoclonal antibody (OKT3/5C3), phytohemagglutinin (PHA), and unstimulated blood. Lithium, alone and in combination with any of the tested antidepressants, led to a consistent increase of IL-1ß, IL-6 and TNF-α levels in the unstimulated as well as the stimulated blood. In the OKT3/5C3- and PHA-stimulated blood, IL-17 production was significantly enhanced by lithium. Lithium additionally increased IL-2 concentrations significantly in PHA-stimulated blood. The data support the view that lithium has pro-inflammatory properties. These immunological characteristics may contribute to side effects of lithium, but may also explain its beneficial effects in patients suffering from HIV infection or SLE.

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Section: Discussionmentioning

confidence: 99%

Impact of lithium alone and in combination with antidepressants on cytokine production in vitro

et al. 2014

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“…Interleukin-6 and TNF-a facilitate the breakdown of serotonin, decreasing its levels in the brain [27]. Anti-TNF-a medications have anti-depressive effects in studies, potentially by enhancing serotonergic or noradrenergic neurotransmission and normalizing stress hormone secretion [28].…”

Section: Inflammatory Mediators In Depressionmentioning

confidence: 99%

Psoriasis, Depression, and Inflammatory Overlap: A Review

et al. 2017

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Psoriasis has an enormous impact on patients' lives and is frequently associated with depression. Depression in psoriasis may be attributed, at least in part, to elevated proinflammatory cytokines rather than the psychosocial impact of psoriasis itself. Biologics that target inflammatory cytokines treat the clinical manifestations of psoriasis, but may also play a role in reducing associated depression. Multiple biologics have decreased symptoms of depression during clinical trials in psoriasis; however, these studies used a variety of depression screening tools, which limits comparison. Furthermore, it is difficult to distinguish whether improved depression is the result of the direct anti-inflammatory effect of the biologic, or the indirect effect of improved psoriasis leading to better psychological status. Future studies evaluating depression in patients with psoriasis could benefit from a standardized depression screening tool to mitigate discrepancies and facilitate comparison across treatment types. Here, we highlight the inflammatory overlap between psoriasis and depression by examining the pathophysiology of depression, and reviewing psoriasis clinical studies that assessed depression as an outcome measure.

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“…For example, administration of the peripherally active TNF antagonist etanercept, which does not cross the blood brain barrier (BBB), eliminated depressive-like behavior following chronic mild stress in mice (Krugel et al, 2013). In addition, studies have shown that individual differences in peripheral immune responses (IL-6 responses, in particular) are associated with the susceptibility of laboratory animals to social avoidance after repeated social defeat stress.…”

Section: Immunological Mechanismsmentioning

confidence: 99%

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

Miller

Haroon

Felger

2016

Neuropsychopharmacol

118

124

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A wealth of data has been amassed that details a complex, yet accessible, series of pathways by which the immune system, notably inflammation, can influence the brain and behavior. These data have opened the window to a diverse array of novel targets whose potential efficacy is tied to specific neurotransmitters and neurocircuits as well as specific behaviors. What is clear is that the impact of inflammation on the brain cuts across psychiatric disorders and engages dopaminergic and glutamatergic pathways that regulate motivation and motor activity as well as the sensitivity to threat. Given the ability to identify patient populations with increased inflammation, the precision of interventions can be further tuned, in conjunction with the ability to establish target engagement in the brain through the use of multiple neuroimaging strategies. After a brief overview of the mechanisms by which inflammation affects the brain and behavior, this review examines the extant literature on the efficacy of anti-inflammatory treatments, while forging guidelines for future intelligent clinical trial design. An examination of the most promising therapeutic strategies is also provided, along with some of the most exciting clinical trials that are currently being planned or underway.

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Antidepressant effects of TNF-α blockade in an animal model of depression

Cited by 94 publications

References 51 publications

Impact of lithium alone and in combination with antidepressants on cytokine production in vitro

Impact of lithium alone and in combination with antidepressants on cytokine production in vitro

Psoriasis, Depression, and Inflammatory Overlap: A Review

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

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