[The influence of fluoxetine on neuroimmune interaction in multiple sclerosis]. / Vliyanie fluoksetina na neiroimmunnoe vzaimodeistvie pri rasseyannom skleroze.

OBJECTIVE: To study the effect of fluoxetine on Th17- and Th1-immune response, which plays an important role in the pathogenesis of multiple sclerosis (MS). MATERIAL AND METHODS: Ten patients with relapsing-remitting MS and ten healthy subjects were examined. The functions of Th17- and Th1-immune responses were assessed by the production of cytokines interleukin-17 (IL-17) and interferon-gamma (IFN-γ) by CD4+ T cells stimulated with macrophages or microbeads coated with anti-CD3 and anti-CD28-antibodies. To assess the effect of fluoxetine on the macrophages-induced Th17- and Th1-immune response, macrophages were pre-incubated in the presence of fluoxetine and co-cultured with autologous CD4+ T-cells. In the case of stimulation of CD4+ T-cells with anti-CD3/CD28-microbeads, fluoxetine was added directly to the T-helper cells before adding of microbeads. In addition, we evaluated the effect of fluoxetine on the production of the factors of differentiation of Th17-cells cytokines IL-6 and IL-1ß by macrophages. The levels of cytokines in the cell culture supernatants were measured by ELISA. RESULTS: The production of IL-17 and IFN-γ by CD4+ T-cells stimulated with macrophages or anti-CD3/CD28-microbeads was comparable between the groups. Fluoxetine suppressed the production of IL-17 and IFN-γ by anti-CD/CD28-stimulated CD4+ T-cells in both groups. Fluoxetine also suppressed the production of IL-6 and IL-1ß by macrophages as well as their ability to induce IL-17 and IFN-γ production by CD4+ T-cells in both groups. CONCLUSIONS: Fluoxetine may have an anti-inflammatory effect in MS that could be mediated by suppression of Th17- and Th1-cells or macrophage-induced Th17- and Th1-immune response.

[The role of macrophages in the development of neuroinflammation in multiple sclerosis]. / Rol' makrofagov v razvitii neirovospaleniya pri rasseyannom skleroze.

Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease of the central nervous system with an autoimmune mechanism of development. It is known that along with T- and B-lymphocytes, cells of the innate immune system also play a significant role in the pathogenesis of MS. Macrophages are central to the functioning of the innate immune response and, depending on the phenotype, have pro-and anti-inflammatory properties. In the central nervous system, resident macrophages form microglia capable of presenting antigens and producing cytokines and, depending on phenotype, may participate in the development of autoimmune inflammation or maintaining immunological tolerance. The brief report presents data on the participation of macrophages in the pathogenesis of experimental autoimmune encephalomyelitis and MS. In addition, current methods of modulation of macrophage functions for the treatment of MS are discussed.

[Blockade of D1-like dopaminergic receptors suppresses Th17-cell function in multiple sclerosis]. / Blokada D1-dofaminovykh retseptorov podavlyaet funktsii Th17-kletok pri rasseyannom skleroze.

OBJECTIVE: To investigate the direct effect of D1-like dopaminergic receptors antagonist on Th17-cells function in multiple sclerosis (MS) in vitro. MATERIAL AND METHODS: Forty-one relapsing-remitting MS patients and twenty-five healthy subjects were examined. The functional activity of Th17-cells was assessed by the ability to produce IL-17 and IFN-γ by peripheral blood mononuclear cells (PBMCs) and CD4+ T cells, stimulated with microbeads coated with anti-CD3/anti-CD28-antibodies. To study the involvement of D1-like dopaminergic receptors in modulation of Th17-cell function, the samples of PBMCs or CD4+ T-cells were cultured in the presence of dopamine and/or specific D1-like dopaminergic receptors antagonist (SCH23390). Cytokine levels in cell culture supernatants were measured by ELISA. RESULTS: The production of IL-17 and IFN-γ by stimulated PBMCs were higher in MS patients during relapse than in MS patients during clinical remission or in healthy subjects. The production of cytokines by stimulated PBMCs or CD4+ T-cells in MS patients during clinical remission and healthy subjects was comparable. Dopamine reduced the production of cytokines by PBMCs and CD4+ T-cells in all groups. Blockade of D1-like dopaminergic receptors did not affect the dopamine-mediated cytokine suppression in MS patients and healthy subjects. Blockade of D1-like dopaminergic receptors directly suppressed cytokine production by PBMCs and CD4+ T-cells in MS patients and healthy subjects. CONCLUSIONS: Dopamine and blockade of D1-like dopaminergic receptors have an inhibitory effect on Th17-cell function in MS. The activation of D2-like dopaminergic receptors could mediate the inhibitory effect of dopamine on Th17-cells.

[The prospect of dopaminergic therapy in multiple sclerosis]. / Perspektivy dofaminergicheskoi terapii pri rasseyannom skleroze.

Dopamine is a direct mediator of neuroimmune interactions. Recent studies show that by acting on the dopaminergic receptors, it is possible to modulate Th17-immune response, which play a crucial role in the pathogenesis of multiple sclerosis. Dopamine can modulate Th17 cells function as well as dendritic cell-mediated Th17-immune response that allows considering dopaminergic receptors as a new therapeutic target in multiple sclerosis. In this short communication, the prospects of using dopaminergic therapy as a pathogenetic treatment for multiple sclerosis are discussed.

[The influence of fluoxetine on interleukin-6 and interleukin-1ß production by dendritic cells in multiple sclerosis in vitro]. / Vliyanie fluoksetina na produktsiyu dendritnymi kletkami interleikina-6 i interleikina-1ß pri rasseyannom skleroze in vitro.

THE AIM OF THE STUDY: Was to evaluate the effect of selective serotonin reuptake inhibitor fluoxetine on the production of cytokines interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) by dendritic cells in multiple sclerosis (MS). MATERIAL AND METHODS: 5 patients with relapsing-remitting MS and five healthy subjects were examined. Levels of IL-6 and IL-1ß were measured by ELISA in culture supernatants obtained from lipopolysaccharide stimulated dendritic cells. To assess the effect of fluoxetine on cytokine production, dendritic cells were stimulated in the presence of fluoxetine and antagonists of 5-HT1A-, 5-HT2A-, 5-HT2B-receptors or agonist of 5-HT2B-receptors. RESULTS: Cytokine production by dendritic cells was comparable in both groups. Fluoxetine suppressed IL-6 and IL-1ß production in both groups. Blockade of 5-HT2B-receptors with specific antagonist RS 127445 reduced the inhibitory effect of fluoxetine on IL-1ß production in both groups and IL-6 production in healthy subjects. In contrast, activation of 5-HT2B-receptors by specific agonist BW 723C86 increased the inhibitory effect of fluoxetine on IL-6 production by dendritic cells in both groups, but did not affect on IL-1ß production. CONCLUSION: These data suggest an anti-inflammatory effect of fluoxetine in MS by modulating pro-inflammatory cytokines production by dendritic cells. This effect could be mediate by activation of 5-HT2B-receptors.

[Serotonergic system as a therapeutic target in multiple sclerosis]. / Serotoninergicheskaia sistema kak terapevticheskaia mishen' pri rasseiannom skleroze.

The article presents the current literature on the role of serotonin in immunomodulation in multiple sclerosis, in particular, on the effect of serotonin on Th17-immune response and function of dendritic cells. The role of serotonin in the regulation of the gut-brain axis and the prospects for serotoninergic drugs as pathogenetic therapy in multiple sclerosis are discussed.