Cytokines in Multiple Sclerosis – Possible Targets for Immune Therapies

Trenova, Anastasiya G.; Slavov, G

doi:10.17756/jnen.2016-006

Cited by 6 publications

(6 citation statements)

References 37 publications

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“…Adaptive immunity especially Th1/Th17‐mediated inflammation play a crucial role in the progression of MS and a lot of other autoimmune diseases such as Rheumatoid arthritis, Systemic lupus erythematosus and type I diabetes 7 . Some cytokines are critical components of the immune inflammatory process and impaired production of these cytokines triggers inflammation in the CNS 31 …”

Section: Discussionmentioning

confidence: 99%

“…7 Some cytokines are critical components of the immune inflammatory process and impaired production of these cytokines triggers inflammation in the CNS. 31 Recently, berberine is effective in the regulation of the differentiation of Th1 and Th17 cells and improved the severity of EAE. 32,33 Additionally, berberine can decrease the clinical severity of EAE by reducing BBB permeability, inflammatory cells infiltration into CNS and as a result reducing CNS inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells

Tavaf

Soltanmohammadi

Zargarani

et al. 2023

Immunity Inflam & Disease

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Introduction: Among the most frequent demyelinating autoimmune disorders of the central nervous system (CNS) is multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is used as an animal model of multiple sclerosis. Berberine is an alkaloid found in some medicinal plants with anti-inflammatory effects. Methods: C57BL/6 female mice were used and divided into three groups: (1) The control group received PBS, (2) the low-dose treatment group received 10 mg/kg of berberine, and (3) The high-dose treatment group received 30 mg/kg of berberine.Myelin Oligodendrocyte Glycoprotein and complete Freund's adjuvant were subcutaneously administered to induce EAE. Mice were given intraperitoneal injections of pertussis toxin on the day of immunization and 2 days later.Histological studies showed low lymphocyte infiltration and demyelination of CNS in the treated groups. Results:The clinical scores of the treatment group with low-dose berberine (T1: 2 ± 0.13) and high-dose berberine (T2: 1.5 ± 0.14) were significantly (p < .001) lower than the control group (CTRL: 4.5 ± 0.13). Treatment groups decreased proinflammatory cytokines (IFN-γ, TNF-α, interleukin [IL]-17) (p < .001) as well as increased anti-inflammatory cytokine expression (IL-4, IL-10, IL-27, IL-33, IL-35, TGF-β) (p < .01) when compared to the CTRL group. Treatment groups with berberine reduced expression of the Th1 and Th17 cytokines and transcription factors (p < .001) and increased expression of transcription factors and Th2 and Treg cytokines (p < .01) in contrast to CTRL group. Conclusion:Berberine appears to have a protective effect on disease development and alleviating disease status in EAE, which appears to be due

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells

Tavaf

Soltanmohammadi

Zargarani

et al. 2023

Immunity Inflam & Disease

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“…Although the precise pathophysiology still remains to be clarified, oxidative stress is known to play a major role in the development of the disease (Rajda et al, 2017). Beside this, blood brain barrier (BBB) disruption and immune system dysregulation (Høglund and Maghazachi, 2014), pro-and anti-inflammatory cytokine disequilibrium (Trenova and Slavov, 2015) and activation of glial cells (Ponath et al, 2018) were described to be important too. As in the animal models of MS, in the human disease, mature oligodendrocytes (OLGs) are already affected at the onset of the disease.…”

Section: Introductionmentioning

confidence: 99%

Cuprizone markedly decreases kynurenic acid levels in the rodent brain tissue and plasma

Polyák

Cseh

Bohár

et al. 2021

Heliyon

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Background: The kynurenine (KYN) pathway (KP) of the tryptophan (TRP) metabolism seems to play a role in the pathomechanism of multiple sclerosis (MS). Cuprizone (CPZ) treated animals develop both demyelination (DEM) and remyelination (REM) in lack of peripheral immune response, such as the lesion pattern type III and IV in MS, representing primary oligodendrogliopathy. Objective: To measure the metabolites of the KP in the CPZ treated animals, including TRP, KYN and kynurenic acid (KYNA). We proposed that KYNA levels might be decreased in the CPZ-induced demyelinating phase of the animal model of MS, which model represents the progressive phase of the disease. Methods: A total of 64 C57Bl/6J animals were used for the study. Immunohistochemical (IHC) measurements were performed to prove the effect of CPZ, whereas high-performance liquid chromatography (HPLC) was used to quantify the metabolites of the KP (n ¼ 10/4 groups; DEM, CO1, REM, CO2). Results: IHC measurements proved the detrimental effects of CPZ. HPLC measurements demonstrated a decrease of KYNA in the hippocampus (p < 0.05), somatosensory cortex (p < 0.01) and in plasma (p < 0.001). Conclusion: This is the first evidence of marked reduction in KYNA levels in a non-immune mediated model of MS. Our results suggest an involvement of the KP in the pathomechanism of MS, which needs to be further elucidated.

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“…Neuronal damage and neuroglial activation could cause the secretion of various cytokines which are involved in differentiation of Th1, Th2, Th9, and Th17 lymphocytes (6). Studies have shown changes in various cytokines level in serum and cerebrospinal fluid (CSF) of MS patients as compared to controls (7–9).…”

Section: Introductionmentioning

confidence: 99%

Computational Intelligence Technique for Prediction of Multiple Sclerosis Based on Serum Cytokines

et al. 2019

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Multiple sclerosis (MS) is a neurodegenerative disease characterized by lesions in the central nervous system (CNS). Inflammation and demyelination are the leading causes of neuronal death and brain lesions formation. The immune reactivity is believed to be essential in the neuronal damage in MS. Cytokines play important role in differentiation of Th cells and recruitment of auto-reactive B and T lymphocytes that leads to neuron demyelination and death. Several cytokines have been found to be linked with MS pathogenesis. In the present study, serum level of eight cytokines (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, and TNF-α) was analyzed in USA and Russian MS to identify predictors for the disease. Further, the model was extended to classify MS into remitting and non-remitting by including age, gender, disease duration, Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) into the cytokines datasets in Russian cohorts. The individual serum cytokines data for the USA cohort was generated by Z score percentile method using R studio, while serum cytokines of the Russian cohort were analyzed using multiplex immunoassay. Datasets were divided into training (70%) and testing (30%). These datasets were used as an input into four machine learning models (support vector machine, decision tree, random forest, and neural networks) available in R programming language. Random forest model was identified as the best model for diagnosis of MS as it performed remarkable on all the considered criteria i.e., Gini, accuracy, specificity, AUC, and sensitivity. RF model also performed best in predicting remitting and non-remitting MS. The present study suggests that the concentration of serum cytokines could be used as prognostic markers for the prediction of MS.

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Cytokines in Multiple Sclerosis – Possible Targets for Immune Therapies

Cited by 6 publications

References 37 publications

Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells

Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells

Cuprizone markedly decreases kynurenic acid levels in the rodent brain tissue and plasma

Computational Intelligence Technique for Prediction of Multiple Sclerosis Based on Serum Cytokines

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