[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.

[Prospects for the use of polyphenols in multiple sclerosis]. / Perspektivy primeneniya polifenolov pri rasseyannom skleroze.

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease. Therapy for MS does not always slow down the progression of the disease. In many cases, pathogenetic therapy of MS leads to serious side-effects, in particular, to immunosuppression, limiting using of various disease modifying therapy (DMT) in MS. In this regard, it is important to study the potential use of drugs that have immunomodulatory and neuroprotective effects, as well as a favorable safety profile. Polyphenols (compounds containing phenolic and hydroxyl groups, often of natural origin) have the ability to modulate immunoregulatory targets, reducing the production of various pro-inflammatory cytokines that play an important role in the pathogenesis of MS. The combined use of DMT and substances with a favorable safety profile, anti-inflammatory activity, and the ability to penetrate the blood-brain barrier, such as polyphenols, may be one of the promising strategies in the treatment of MS to improve the quality of life of patients. In this review, we consider the mechanisms of action of polyphenols in MS, their application in experimental models of MS, and the results of clinical studies of polyphenols in MS.

[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.