The role of dopamine in modulation of Th-17 immune response in multiple sclerosis

Melnikov, Mikhail; Belousova, Olga; Муругин, В В; Pashenkov, Мikhail; Boyко, Alexey

doi:10.1016/j.jneuroim.2016.01.020

Cited by 49 publications

(53 citation statements)

References 38 publications

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“…Inflammation is also associated with changes in brain dopamine metabolism (Felger, 2016); dopamine in turn affects immune system, especially immune response mediated by interleukin 17 producing Th cells (labelled Th17) that are distinct from Th1 and Th2 cells (Lieberknecht et al, 2016; Melnikov et al, 2016). Bupropion, a non-serotonergic antidepressant, inhibits dopamine reuptake, increases brain extracellular dopamine concentration (Ascher et al, 1995; Cremers et al, 2016), and has been shown to reduce inflammation mediated by both Th1 (by reducing IL-1 beta, IFNγ, and TNFα) and Th17 cells (Brustolim et al, 2006; Ebbinghaus et al, 2012; Warner-Schmidt et al, 2011).…”

Section: 0 Introductionmentioning

confidence: 99%

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Jha

Minhajuddin

Gadad

et al. 2017

Psychoneuroendocrinology

160

113

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Objective Currently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed. Method Subjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n=51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n=55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro™ human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants. Results The treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1 mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient=−0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient=0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for <1 mg/L and Bupropion-SSRI for ≥1 mg/L) was 53.1%, with a number needed to treat of 8.6. Side effect burden was unrelated to any baseline inflammatory marker. Conclusions Baseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder.

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Section: 0 Introductionmentioning

confidence: 99%

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Jha

Minhajuddin

Gadad

et al. 2017

Psychoneuroendocrinology

160

113

View full text Add to dashboard Cite

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“…These inflammatory changes may result in reduced synthesis of dopamine by diversion of tetrahydrobiopterin, an essential cofactor of NOS and tyrosine hydroxylase, away from rate limiting step (conversion of tyrosine to L-3,4-dihydroxyphenylalanine) in dopamine synthesis [reviewed in detail by Miller et al (19)]. On the contrary, increasing dopamine, in cultured human peripheral blood mononuclear cells, suppresses IL-17 levels (20). Similarly, pramipexole, a dopamine agonist, inhibits production of IL-17 in animal models of experimental autoimmune encephalitis (21).…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, pramipexole, a dopamine agonist, inhibits production of IL-17 in animal models of experimental autoimmune encephalitis (21). Furthermore, use of antipsychotic medications that block dopamine receptors such as amisulpiride (20), chlorpromazine, haloperidol, clozapine, and quetiapine (22) has been associated with elevated IL-17 levels in humans. Bupropion, an antidepressant medication that inhibits dopamine reuptake and stimulates presynaptic release of dopamine and norepinephrine (23–25), has been shown to reduce IL-17 mediated inflammatory response and joint swelling in the murine antigen-induced arthritis model (26).…”

Section: Introductionmentioning

confidence: 99%

Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection

Jha

Minhajuddin

Gadad

et al. 2017

Brain, Behavior, and Immunity

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Background Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells and has been implicated in pathophysiology of depression. IL-17 putatively disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine has been shown to decrease Th17 cell-mediated immune response. Nevertheless, whether IL-17 can predict differential treatment outcome with antidepressants modulating dopaminergic transmission is unknown. Methods IL-17 and other T cell and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the Bioplex Pro™ human cytokine 27-plex kit in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided baseline plasma and were treated with either bupropion plus escitalopram (bupropion-SSRI), escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine (n=166). Differential changes in symptom severity and side-effects based on levels of IL-17 and other T and non-T cell markers were tested using a treatment-arm-by-biomarker interaction in separate repeated measures mixed model analyses. Subsequent analyses stratified by treatment arm were conducted for those markers with a significant interaction. Results There was a significant treatment-arm-by- IL-17 interaction for depression severity (p=0.037) but not for side-effects (p=0.28). Higher baseline IL-17 level was associated with greater reduction in depression severity (effect size=0.78, p=0.008) in the bupropion-SSRI but not the other two treatment arms. Other T and non-T cell markers were not associated with differential treatment outcomes. Conclusion Higher baseline levels of IL-17 are selectively associated with greater symptomatic reduction in depressed patients treated with bupropion-SSRI combination.

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“…a T-helper cell subset producing IL-17, are thought to play a pivotal role in MS pathogenesis [29] . We have recently shown that MS exacerbation is characterized by decreased concentrations of DA in serum and a concomitant increase in the percentages of Th17 cells and the production of interleukin-17 (IL-17) and IFN-γ by PBMCs [30] . We also found that DA suppressed IL-17 and IFN-γ production by PBMCs from MS patients and healthy subjects, and this suppressive effect of DA was abolished in the presence of an antagonist of D2-like receptors (sulpiride) [30] .…”

Section: Introductionmentioning

confidence: 99%

“…We have recently shown that MS exacerbation is characterized by decreased concentrations of DA in serum and a concomitant increase in the percentages of Th17 cells and the production of interleukin-17 (IL-17) and IFN-γ by PBMCs [30] . We also found that DA suppressed IL-17 and IFN-γ production by PBMCs from MS patients and healthy subjects, and this suppressive effect of DA was abolished in the presence of an antagonist of D2-like receptors (sulpiride) [30] . Here we extended our study in order to examine relationships between Th17 cells and three other biogenic amines, such as NE, epinephrine (EPI) and serotonin (SE), in MS patients and healthy donors.…”

Section: Introductionmentioning

confidence: 99%

The Role of Biogenic Amines in the Regulation of Interaction between the Immune and Nervous Systems in Multiple Sclerosis

Boyko

Melnikov

Zhetishev

et al. 2016

Neuroimmunomodulation

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Objective: Multiple sclerosis (MS) is a demyelinating, presumably autoimmune disease of the central nervous system. Biogenic amines may participate in MS pathogenesis modulating immune cell activity and cytokine production. Methods: Forty-three patients with relapsing-remitting MS were examined. Serotonin (SE), norepinephrine (NE) and epinephrine (EPI) concentrations in sera were measured by ELISA. The functional activity of Th17 and Th1 cells was assessed by the ability of peripheral blood mononuclear cells (PBMCs) to produce interferon-gamma (IFN-γ) and interleukin-17 (IL-17) and cell proliferation upon stimulation with microbeads coated with anti-CD3 and anti-CD28 antibodies. To evaluate the effect of biogenic amines on Th17 and Th1 cells, PBMCs were cultured in the presence of SE and NE. Statistical analysis was performed using Prism 6 software. Results: Concentrations of SE and EPI in sera were not different between the groups. Concentrations of NE in sera from MS patients were lower than those in the healthy control group. The production of IL-17 and IFN-γ in MS patients in relapse was higher than that in patients in remission or in the control group. SE at a concentration of 10^-4M suppressed IL-17 production. NE at a concentration of 10^-4M suppressed both IL-17 and IFN-γ production. Conclusions: These data suggest an anti-inflammatory role for biogenic amines in MS.

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The role of dopamine in modulation of Th-17 immune response in multiple sclerosis

Cited by 49 publications

References 38 publications

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial

Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection

The Role of Biogenic Amines in the Regulation of Interaction between the Immune and Nervous Systems in Multiple Sclerosis

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