The role of macrophages in anti-inflammatory activity of antidepressant drugs

Nazimek, Katarzyna; Strobel, Spencer; Bryniarski, Paweł; Kozlowski, Michael; Filipczak-Bryniarska, Iwona; Bryniarski, Krzysztof

doi:10.1016/j.imbio.2016.07.001

Cited by 73 publications

(48 citation statements)

References 98 publications

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“…Furthermore, it is assumed that the inclusion of antidepressants in the complex therapy of depression may alleviate chronic inflammation [19]. In a study conducted with post-stroke patients, it was reported that elevated P/L ratios may be predictive as an independent marker for the development of depression [20]. In this current study, the P/L ratio was found to be higher in patients with major depression compared to the control group.…”

Section: Discussionsupporting

confidence: 47%

Neutrophil/Lymphocyte ratio in patients with major depression and the impact of electroconvulsive therapy

2020

Ann Clin Anal Med

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Aim: An accumulation of evidence supports the role of inflammation in the etiology of depression, particularly in severe depression. In this study, we aimed to investigate the effect of electroconvulsive therapy (ECT) treatment on the rates of neutrophil/lymphocytes (N/L), platelets/lymphocyte (P/L) which are subclinical inflammatory markers in patients with moderate/severe depression who went into remission. Materials and Methods: Patients with major depression who had been admitted to hospital in the preceding 2 years with a diagnosis of major depression according to DSM 5 and who had undergone ECT were included in this study as well as a similar number of patients were included as a control group. The groups were compared with respect to the subclinical inflammatory markers N/L, P/L at baseline and after ECT. Fifty-seven patients were compared with respect to N/L, P/L ratios before and after ECT. Results: A total of 116 patients were included in the study, of whom 57 had major depression and 59 were in the control group. The N/L values were significantly higher in the pre-ECT patient group compared to the control group. The post-ECT N/L value was significantly higher compared to the control group and no difference was found between the P/L ratios. There was no significant difference between pre and post-ECT N/L, P/L values in the patient group. Discussion: This study suggests the presence of subclinical inflammation in moderate to severe major depression patients which persists after ECT. Largescale studies are needed to determine the effects of ECT on inflammation.

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Section: Discussionsupporting

confidence: 47%

Neutrophil/Lymphocyte ratio in patients with major depression and the impact of electroconvulsive therapy

2020

Ann Clin Anal Med

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“…For example, it influences diseases like gut inflammation (109), allergic asthma (110), rheumatoid arthritis (111), and neuroinflammation such as ALS (60) and autism (112). In the recent years, we could observe the anti-inflammatory effects of antidepressant (influencing serotonin levels in the body) in clinical practice that are, for example, mediated via macrophage modulation (113). Serotonin seems to be a promising new target when it comes to modulating immune responses.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Serotonin in Immune Cells

Herr

Bode

Duerschmied

2017

Front. Cardiovasc. Med.

337

298

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Serotonin [5-hydroxytryptamine (5-HT)] plays an important role in many organs as a peripheral hormone. Most of the body’s serotonin is circulating in the bloodstream, transported by blood platelets and is released upon activation. The functions of serotonin are mediated by members of the 7 known mammalian serotonin receptor subtype classes (15 known subtypes), the serotonin transporter (SERT), and by covalent binding of serotonin to different effector proteins. Almost all immune cells express at least one serotonin component. In recent years, a number of immunoregulatory functions have been ascribed to serotonin. In monocytes/macrophages, for example, serotonin modulates cytokine secretion. Serotonin can also suppress the release of tumor necrosis factor-α and interleukin-1β by activating serotonin receptors. Furthermore, neutrophil recruitment and T-cell activation can both be mediated by serotonin. These are only a few of the known immunomodulatory roles of serotonin that we will review here.

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“…This is true also for anti‐inflammatory agents (Rosenblat et al, ). Hence, monocytes/macrophages together with their counterpart in the CNS, microglia, can be considered the bridge between inflammation and depression (Nazimek et al, ). In fact, the expression of genes involved in inflammation and immunity are up‐regulated in monocytes from MDD patients compared to healthy volunteers (Grosse et al, ), while glucocorticoid receptor expression is reduced (Carvalho et al, ).…”

Section: Introductionmentioning

confidence: 99%

Vortioxetine exerts anti‐inflammatory and immunomodulatory effects on human monocytes/macrophages

Talmon

Rossi

Pastore

et al. 2017

British J Pharmacology

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BACKGROUND AND PURPOSEA crosstalk between the immune system and depression has been postulated, with monocytes/macrophages and cytokines having a key role in this interaction. In this study, we examined whether vortioxetine, a multimodal anti-depressive drug, was endowed with anti-inflammatory and antioxidative activity, leading to immunomodulatory effects on human monocytes and macrophages. EXPERIMENTAL APPROACHHuman monocytes were isolated from buffy coats and used as such or differentiated into M1 and M2 macrophages. Cells were treated with vortioxetine before or after differentiation, and their responsiveness was evaluated. This included oxy-radical and TNFα production, TNFα and PPARγ gene expression and NF-κB translocation. KEY RESULTSVortioxetine significantly reduced the PMA-induced oxidative burst in monocytes and in macrophages (M1 and M2), causing a concomitant shift of macrophages from the M1 to the M2 phenotype, demonstrated by a significant decrease in the expression of the surface marker CD86 and an increase in CD206. Moreover, treatment of monocytes with vortioxetine rendered macrophages derived from this population less sensitive to PMA, as it reduced the oxidative burst, NF-kB translocation, TNFα release and expression while inducing PPARγ gene expression. FACS analysis showed a significant decrease in the CD14 + /CD16 + /CD86 + M1 population. CONCLUSIONS AND IMPLICATIONSThese results demonstrate that in human monocytes/macrophages, vortioxetine has antioxidant activity and anti-inflammatory effects driving the polarization of macrophages towards their alternative phenotype. These findings suggest that vortioxetine, alongside its antidepressive effect, may have immunomodulatory properties. Abbreviations

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The role of macrophages in anti-inflammatory activity of antidepressant drugs

Cited by 73 publications

References 98 publications

Neutrophil/Lymphocyte ratio in patients with major depression and the impact of electroconvulsive therapy

Neutrophil/Lymphocyte ratio in patients with major depression and the impact of electroconvulsive therapy

The Effects of Serotonin in Immune Cells

Vortioxetine exerts anti‐inflammatory and immunomodulatory effects on human monocytes/macrophages

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