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Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Published on: July 4, 2007
Dietary phytol reduces clinical symptoms in experimental autoimmune encephalomyelitis (EAE) at least partially by
Leonard Blum1, Nadja Tafferner2, Ilknur Spring2
1pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany.
Abstract:
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system. We investigated the effect of phytol in an animal model of MS, experimental autoimmune encephalomyelitis (EAE), as phytol, a plant-derived diterpene alcohol, exerts anti-inflammatory and redox-protective actions. We observed a significant amelioration of clinical symptoms in EAE C57BL/6N mice fed prophylactically with a phytol-enriched diet. Demyelination, DNA damage, and infiltration of immune cells, specifically TH1 cells, into the central nervous system were reduced in phytol-fed EAE mice. Furthermore, phytol reduced T-cell proliferation ex vivo. Phytanic acid - a metabolite of phytol - also reduced T-cell proliferation, specifically that of TH1 cells. Additionally, phytol-enriched diet increased the mRNA expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 2 in white blood cells in the lymph nodes. Accordingly, phytol lost its anti-inflammatory effects in chimeric EAE C57BL/6N mice whose peripheral cells lack NOX2, indicating that phytol mediates its effects in peripheral cells via NOX2. Moreover, the effects of phytol on T-cell proliferation were also NOX2-dependent. In contrast, the T-cell subtype alterations and changes in proliferation induced by phytanic acid, the primary metabolite of phytol, were NOX2-independent. In conclusion, phytol supplementation of the diet leads to amelioration of EAE pathology in both a NOX2-dependent and a NOX2-independent manner via yet unknown mechanisms.
Key Messages:
Phytol diet ameliorates EAE pathology. Phytol diet reduces demyelination, immune cell infiltration, and T-cell proliferation. Phytol diet increases NOX2 mRNA expression in white blood cells in the lymph nodes. Phytol mediates its effects in peripheral cells via NOX2. Effects of phytol on T-cell proliferation were NOX2-dependent.
Insights
Phytol, a plant compound, significantly improved symptoms in an animal model of multiple sclerosis (MS). This dietary supplement reduced central nervous system damage and immune cell activity, offering a potential therapeutic avenue for MS.
Area of Science:
- Neuroimmunology
- Inflammation Research
- Natural Product Chemistry
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
- Phytol, a diterpene alcohol found in plants, possesses known anti-inflammatory and redox-protective properties.
- Investigating natural compounds like phytol offers potential therapeutic strategies for autoimmune diseases.
Purpose of the Study:
- To investigate the therapeutic potential of phytol in experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
- To elucidate the mechanisms underlying phytol's effects, including its impact on immune cell activity and the role of NOX2.
- To assess the effects of phytol and its metabolite, phytanic acid, on T-cell responses.
Main Methods:
- EAE was induced in C57BL/6N mice, with some fed a prophylactic phytol-enriched diet.
- Clinical symptoms, demyelination, DNA damage, and immune cell infiltration were assessed.
- T-cell proliferation was measured ex vivo, and NOX2 expression in white blood cells was analyzed.
- Chimeric mice lacking NOX2 in peripheral cells were used to determine the role of NOX2.
Main Results:
- Phytol-enriched diet significantly ameliorated clinical symptoms and reduced demyelination and DNA damage in EAE mice.
- Phytol and phytanic acid reduced T-cell proliferation, particularly TH1 cells.
- Phytol increased NOX2 mRNA expression in lymph node white blood cells, and its anti-inflammatory effects were NOX2-dependent.
- Phytanic acid's effects on T-cell proliferation were NOX2-independent.
Conclusions:
- Dietary phytol ameliorates EAE pathology by reducing central nervous system inflammation and immune cell infiltration.
- Phytol exerts its anti-inflammatory and immunomodulatory effects through both NOX2-dependent and NOX2-independent pathways.
- Phytol and its metabolite phytanic acid show potential in modulating T-cell responses relevant to MS pathogenesis.
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