Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis

Abstract

Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CCL-2), CCL-3, IL-1 receptor antagonist, IL-13, IL-17, IL-5, IL-7, and the soluble IL-2 receptor were measured in at least three datasets and thus were meta-analyzed. Antidepressant treatment significantly decreased peripheral levels of IL-6 (Hedges g = -0.454, P <0.001), TNF-α (g = -0.202, P = 0.015), IL-10 (g = -0.566, P = 0.012), and CCL-2 (g = -1.502, P = 0.006). These findings indicate that antidepressants decrease several markers of peripheral inflammation. However, this meta-analysis did not provide evidence that reductions in peripheral inflammation are associated with antidepressant treatment response although few studies provided separate data for treatment responders and non-responders.

The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

“…Therefore, the serum levels of TNF-α, IL-6, IL-10, BDNF, 8-OHdG, and serotonin were measured in this trial and were correlated with HAM-D score to evaluate the effect of the medications. A previous study had found that serum levels of TNF-α, IL-6, IL-10, and 8-OHdG were elevated in patients with MDD [13]. Similarly, we found that the serum levels of TNF-α, IL-6, IL-10, and 8-OHdG were high at baseline and decreased after treatment.…”

“…Furthermore, it has been reported that these proinflammatory cytokines are predominantly elevated in MDD [11]. One of the most substantial anti-inflammatory cytokines is IL-10, which possesses an inhibitory action on proinflammatory cytokines [12,13]. Furthermore, individuals with MDD show a significantly higher level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage, than controls [14,15].…”

SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

“…Plasma CRP and cytokine levels in our sample were consistent with those of other studies exploring inflammation depressed patients but there was a high variability between Ala‐carriers and Val/Val‐carriers for these parameters.…”

“…Rosuvastatin response in this pathology could be modulated by the in Ala‐ or Val/Val‐carrier patients. Likewise, several clinical and preclinical observations suggest that MDD also involves an inflammatory dimension, which could be influenced by antidepressant treatment . Thus, it was tempting to speculate that polymorphisms of the SOD2 gene, by modulating the inflammatory processes, could also modulate the response to antidepressants in MDD.…”

The interplay between depression and tuberculosis

“…Antidepressant therapy has been associated with altered immune functions . For example, previous meta‐analyses have indicated that antidepressant drugs treatment may decrease circulating levels of IL‐1β and IL‐6, TNF‐α, and the C‐C motif ligand 2 chemokine . However, considering the high degree of heterogeneity in those pro‐inflammatory mediators, it is difficult to conclude whether antidepressant drugs contribute or not to the therapeutic benefits through immuno‐inflammatory pathways .…”