Norepinephrine is a neurotransmitter that also has an immunomodulatory effect and is involved in multiple sclerosis (MS) pathogenesis. This study aimed to clarify the role of the β2-adrenoreceptor in the norepinephrine-mediated modulation of interleukin-17 (IL-17) and interferon-γ (IFN-γ) production, which play a critical pathogenetic role in MS. CD4+ T cells obtained from twenty-five relapsing-remitting MS patients and sixteen healthy subjects were cultured ex vivo with norepinephrine and/or β2-adrenoreceptor antagonist or agonist, followed by a cytokine production analysis using ELISA. Norepinephrine suppressed IL-17 and IFN-γ production by the anti-CD3/anti-CD28-microbead-stimulated CD4+ T cells in both groups. Blockade of the β2-adrenoreceptor with the specific antagonist ICI 118.551 enhanced norepinephrine-mediated IL-17 suppression but decreased its inhibitory effect on IFN-γ production in MS patients. In contrast, the β2-adrenoreceptor agonist formoterol did not influence norepinephrine’s inhibitory effect on cytokine production in both groups. The blockade of the β2-adrenoreceptor, even in the absence of exogenous norepinephrine, suppressed IL-17 production but did not influence IFN-γ production in both groups. Conversely, β2-adrenoreceptor activation by formoterol decreased IFN-γ production and did not affect IL-17 production in both groups. These data illustrate the inhibitory effect of norepinephrine on IL-17 and IFN-γ production by CD4+ T cells in MS. The inhibitory effect of norepinephrine on IFN-γ production by CD4+ T cells in MS could be mediated via β2-adrenoreceptor activation.

Depression is one of the most common neuropsychological symptoms of multiple sclerosis. However, in addition to mood disorder, depression can also influence on multiple sclerosis course. The mechanism of this dependence is not fully understood. The recent studies suggest the possible common immune mechanisms in the pathogenesis of depression and multiple sclerosis. In particular, it was shown that along with biogenic amines disturbance, neuroinflammation also play an important role in the pathogenesis of depression. Significant attention is drawn to Th17-cells subsets, which are considered as critical players in the pathogenesis of inflammatory diseases of the central nervous system, including multiple sclerosis. This brief report reviews the literature data on the role of neuroinflammation in the reciprocal influence of multiple sclerosis and depression with focus on Th17-cells, which may underlie pathogenetic mechanisms of both this diseases.

Investigation of neuroimmune interactions is one of the most developing areas in the study of multiple sclerosis pathogenesis. Recent evidence suggests the possibility of modulating neuroinflammation by targeting biogenic amine receptors. It has been shown that selective serotonin reuptake inhibitor fluoxetine modulates innate and adaptive immune system cells' function and can reduce experimental autoimmune encephalomyelitis and multiple sclerosis severity. This brief report discusses the immune mechanisms underlying the multiple sclerosis pathogenesis and the influence of fluoxetine on them. The retrospective data on the impact of fluoxetine treatment on the course of multiple sclerosis are also presented. The results of this and other studies suggest that fluoxetine could be considered an additional therapy to the standard first-line disease-modifying treatment for relapsing–remitting multiple sclerosis.

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