The Effect of Antidepressant Medication Treatment on Serum Levels of Inflammatory Cytokines: A Meta-Analysis

Abstract

Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFa), interleukin-6 (IL-6), and IL-1 beta , are elevated in subjects with major depressive disorder (MDD). The reason why this occurs is unclear. Elevated levels of inflammatory cytokines could be a result of brain dysfunction in MDD. It is also possible that inflammatory cytokines contribute to depressive symptoms in MDD. If the first assumption is correct, one would expect levels to normalize with resolution of the depressive episode after treatment. Several studies have measured changes in cytokine levels during antidepressant treatment; however, the results vary. The purpose of this study was to pool all available data on changes in serum levels of TNFa, IL-6, and IL-1b during antidepressant treatment to determine whether these levels change. Studies were included if they used an approved pharmacological treatment for depression, patients had a diagnosis of MDD, and serum levels of TNFa, IL-6, and/or IL-1b were measured before and after treatment. Twenty-two studies fulfilled these criteria. Meta-analysis of these studies showed that, overall, while pharmacological antidepressant treatment reduced depressive symptoms, it did not reduce serum levels of TNFa. On the other hand, antidepressant treatment did reduce levels of IL-1b and possibly those of IL-6. Stratified subgroup analysis by class of antidepressant indicated that serotonin reuptake inhibitors may reduce levels of IL-6 and TNFa. Other antidepressants, while efficacious for depressive symptoms, did not appear to reduce cytokine levels. These results argue against the notion that resolution of a depressive episode is associated with normalization of levels of circulating inflammatory cytokines; however, the results are consistent with the possibility that inflammatory cytokines contribute to depressive symptoms and that antidepressants block the effects of inflammatory cytokines on the brain.

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays

“…An inflammatory cytokine could be a sensitive biomarker for a depressive mood even in healthy subjects (Katsuura et al, 2011). It is also possible that such a cytokine could contribute to the depressive symptoms, and its use as a biomarker could even reveal how antidepressants block the effects of inflammation on the brain (Hannestad et al, 2011;Hernandez et al, 2013). However, a lack of reliability in the measurements weakens the use of multiplex assays for clinical purposes.…”

A Dialogue between the Immune System and Brain, Spoken in the Language of Serotonin

“…129 Finally, SSRI treatment has been shown to normalize elevated cytokine levels in depressed patients. 130 Another link between immune function and SSRI action arises from findings that reduced lymphocyte SERT expression in patients with MDD is normalized by administration of SSRIs. 131 A caveat to a mechanistic interpretation of these studies is the possibility that the actions of SSRIs in immune system function may be mediated by proteins other than SERT, particularly when the evidence derives from in vitro studies of cell suspensions where blockade of the transporter is unlikely to elevate extracellular 5-HT to an extent that would impact cell-surface 5-HT receptors in the way we expect in intact systems.…”

Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

“…For example, rodent pups separated from their mothers later showed more depressive-like symptoms and lower prefrontal cortex parvalbumin levels (a GABAergic marker) compared to unchallenged pups (Leussis et al, 2012), and these differences were reduced by the administration of an anti-inflammatory cyclo-oxygenase 2 (COX-2) inhibitor (Brenhouse and Andersen, 2011b) or anti-inflammatory IL-10 (Wieck et al, 2013). More indirectly, physical exercise and anti-depressant medications have antiinflammatory effects (Gleeson et al, 2011;Hannestad et al, 2011) and they have both appeared to buffer the effects of early-life stress on brain and behavioral outcomes (Harrison and Baune, 2014).…”