[Blockade of D1-like dopaminergic receptors suppresses Th17-cell function in multiple sclerosis].

Objective: To investigate the direct effect of D ₁ -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 D ₁ -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 D ₁ -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 D ₁ -like dopaminergic receptors did not affect the dopamine-mediated cytokine suppression in MS patients and healthy subjects. Blockade of D ₁ -like dopaminergic receptors directly suppressed cytokine production by PBMCs and CD4 ⁺ T-cells in MS patients and healthy subjects.
Conclusions: Dopamine and blockade of D ₁ -like dopaminergic receptors have an inhibitory effect on Th17-cell function in MS. The activation of D ₂ -like dopaminergic receptors could mediate the inhibitory effect of dopamine on Th17-cells.