Dopamine favors expansion of glucocorticoid-resistant IL-17-producing T cells in multiple sclerosis.

Dopamine (DA) is a neurotransmitter produced mainly in the central nervous system (CNS) that has immunomodulatory actions on T cells. As the multiple sclerosis (MS) has long been regarded as an autoimmune disease of CNS mediated by T cells, the objective of this study was to evaluate the impact of DA on in vitro functional status of T cells from relapsing-remitting (RR)-MS patients. Peripheral T-cells from RR-MS patients were activated by mitogens and cell proliferation and cytokine production were assayed by [(3)H]-thymidine uptake and ELISA, respectively. Our results demonstrated that DA enhanced in vitro T cell proliferation and Th17-related cytokines in MS-derived cell cultures. In addition, this catecholamine reduced Treg-related cytokines (IL-10 and TGF-ß) release by activated CD4(+) T cells. These DA-induced effects on T cells were mainly dependent on IL-6 production by both polyclonally-activated CD4(+) T cells and LPS-stimulated monocytes. Furthermore, the production of IL-17 and IL-6 by MS-derived T cells was directly related with neurological disability (EDSS score), and the release of these cytokines was less sensitive to glucocorticoid inhibition in MS patients than in control group, mainly after DA addition. In conclusion, our data suggest that DA amplifies glucocorticoid-resistant Th17 phenotype in MS patients, and this phenomenon could be, at least in part, due to its ability to induce IL-6 production by monocytes and CD4(+) T cells.

Assessing the Impact of IL-6 and Serotonin on Pain and Symptomatology in Fibromyalgia: An Exploratory Clinical Study.

BACKGROUND AND OBJECTIVES: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome characterized by widespread pain and a variety of other symptoms, including fatigue, cognitive dysfunction, and sleep disturbances. Recent research has highlighted the potential role of pro-inflammatory cytokines and neurotransmitters in the pathophysiology of FM. This study aimed to investigate the relationship between serum levels of interleukin-6 (IL-6) and serotonin with the clinical parameters observed in patients with fibromyalgia. Additionally, it sought to analyze the similarities and differences among the different groups classified by symptom severity. MATERIALS AND METHODS: This cross-sectional study included 26 female patients aged 20-70 diagnosed with FM according to the American College of Rheumatology (ACR) 2016 criteria and 14 healthy controls (HCs). Serum levels of IL-6 and serotonin were measured using electrochemiluminescence and high-performance liquid chromatography (HPLC), respectively. RESULTS: FM patients exhibited significantly higher pain scores (VAS), anxiety, and depression levels compared to HCs. FIQ-R scores were significantly elevated in FM patients, with stratification showing 3.8% mild, 65.4% moderate, 23.1% severe, and 7.7% very severe cases. While no significant difference in IL-6 levels was observed between the FM patients and HCs, a trend towards increased IL-6 levels in patients with higher FIQ-R scores was noted. Serum serotonin levels were significantly lower in the FM patients than in the HCs, with moderate patients having lower levels than those classified as severe and very severe. CONCLUSIONS: The study underscores the potential role of IL-6 and serotonin in the pathophysiology of FM, suggesting that these biomarkers could be relevant in assessing the severity and impact of FM. Further research is needed to elucidate these relationships and their implications for developing personalized treatment strategies.

Is Asian type MS an MS phenotype, an NMO spectrum disorder, or a MOG-IgG related disease?

BACKGROUND: A specific particularity of neurological diseases in Asia is the relative commonality of neuromyelitis optica (NMO) and Asian type MS (OSMS). Both conditions also occur in South American patients. The Brazilian population differs from the European and the Asian populations due to the mixture of ancestralities between European colonizers and African slaves. To better know the clinical characteristics of Brazilian patients with Asian type MS this study aimed to analyze the clinical, radiological and serological data that would help to distinguish between OSMS and NMO and clarify, in a Non-Asian population, if OSMS is an MS phenotype, an NMO spectrum disorder by 2015 classification, or a complement activating antibody to myelin oligodendrocyte glycoprotein (MOG-IgG) antibody-related disease. METHODS: We selected cases retrospectively with NMO and OSMS in the medical registry of patients with idiopathic inflammatory demyelinating diseases under follow-up since 1997 in Federal Hospital da Lagoa, the principal reference center for MS treatment in Rio de Janeiro, Brazil. OSMS has selective involvement of the optic nerve and spinal cord with no cerebral or cerebellar symptoms associated with small spinal cord lesions and negativity for the aquaporin-4 antibody (AQP4-IgG). NMO full-filled the revised criteria (2006) associated with longitudinally extensive transverse myelitis (LETM). We recorded the following data: ethnicity/skin color, neurologic impairment "at nadir" and "at recovery" of the index events (optic neuritis and transverse myelitis), long term disability, mortality, health quality of life scores by the SF-36 questionnaire, CSF IgG oligoclonal bands and serological AQP4-IgG and MOG-IgG antibodies tested by Cell-based assay. The last brain MRIs were classified as either satisfying or not satisfying MAGNIMS radiologic criteria for MS or typical or not typical for NMOSD. The new classification of NMO spectrum disorders (2015) was applied. RESULTS: Forty-one OSMS and 122 NMO cases were analyzed. OSMS affected mainly young white women, causing unilateral optic neuritis and partial myelitis with excellent recovery. After a mean disease duration of 20 years, 90% of the patients had free ambulation, and 70% had a mild disability or no disability. Only 7.2% presented a secondary progressive course, and no deaths occurred. All cases had negativity to AQP4-IgG and MOG-IgG biomarkers. 95% had resonance criteria for MS. OSMS differed from NMO by ethnicity, morbidity, and mortality: most were African descendants, with severe motor and visual dysfunction, and one third died. Only NMO cases full-filled the new NMOSD classification (52 AQP4-IgG positive, 29 AQP4-IgG negative, and 41 AQP4-IgG unknown). CONCLUSION: In Brazilian patients, OSMS and NMO are different immune-mediated diseases. OSMS is a milder MS phenotype.

Gait characteristics of multiple sclerosis patients in the absence of clinical disability.

PURPOSE: Motor deficits in lower extremities and gait abnormalities are a major feature of the multiple sclerosis (MS) patients. Patients with minimal clinical disability have subtle gait changes. The aim of this study was to analyze the gait characteristics of MS patients in the absence of clinical disability. METHOD: A case-control study was carried out with 12 MS patients and 12 matched healthy controls. The subjects underwent a clinical neurological evaluation to determine their disability level (EDSS ≤ 1.5). Then, the subjects were referred for completion self-report questionnaires (gait, perceived balance confidence, physical activity and fatigue), gait clinical trials, and 3D kinematic analysis. RESULTS: MS patients showed more impairment of perceived fatigue, perceived of walking impact and perceived balance confidence, despite having no disability. Gait characteristics showed no differences when they were determined by clinical observation. The 3D kinematic analysis of gait showed slight but significant changes in ankle movement. CONCLUSION: MS patients with no clinical disability have discrete changes in gait that can be evidenced by perceived impact on walking and kinematic evaluation, mainly of ankle movement. Moreover, there is a decrease in perceived balance confidence and an increase in perceived fatigue, which are correlated despite having different origins.