Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D3

Mattner, Frank; Smiroldo, Simona; Galbiati, Francesca; Müller, Marc; Lucia, Pietro Di; Poliani, Pietro Luigi; Martino, Gianvito; Panina-Bordignon, Paola; Adorini, Luciano

doi:10.1002/1521-4141(200002)30:2<498::aid-immu498>3.0.co;2-q

Cited by 218 publications

(72 citation statements)

References 55 publications

(48 reference statements)

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“…They occur in almost all tissues of the body and in large numbers in lymphoid organs where they present antigen to T lymphocytes. 1,25-(OH) 2 D inhibits antigen-induced T-lymphocyte proliferation (Bhalla et al, 1984;Lemire & Adams, 1992) and prevents Th1 development in EAE (Mattner et al, 2000). Various reports have shown that 1,25-(OH) 2 D exerts major effects on dendritic cells (DC), by inhibition of DC maturation (Penna & Adorini, 2000;Griffin et al, 2001).…”

Section: Cellular Effectsmentioning

confidence: 84%

“…Treatment with synthetic 1,25-(OH) 2 D analogs has also been reported (Lemire et al, 1994;Mattner et al, 2000;Van Etten et al, 2000Garcion et al, 2003). Curative treatment of vitamin D-deprived rats with the nontoxic-1,25-(OH) 2 D analog MC1288 strongly inhibited EAE symptoms, thus suggesting that these compounds may be a suitable treatment for MS (Garcion et al, 2003).…”

Section: Eae and Vitamin D-related Treatmentmentioning

confidence: 99%

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Multiple sclerosis and vitamin D: an update

et al. 2004

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MS is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS), with an etiology that is not yet fully understood. The prevalence of MS is highest where environmental supplies of vitamin D are lowest. It is well recognized that the active hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH) 2 D), is a natural immunoregulator with anti-inflammatory action. The mechanism by which vitamin D nutrition is thought to influence MS involves paracrine or autocrine metabolism of 25OHD by cells expressing the enzyme 1a-OHase in peripheral tissues involved in immune and neural function. Administration of the active metabolite 1,25-(OH) 2 D in mice and rats with experimental allergic encephalomyelitis (EAE, an animal model of MS) not only prevented, but also reduced disease activity. 1,25-(OH) 2 D alters dendritic cell and T-cell function and regulates macrophages in EAE. Interestingly, 1,25-(OH) 2 D is thought to be operating on CNS constituent cells as well. Vitamin D deficiency is caused by insufficient sunlight exposure or low dietary vitamin D 3 intake. Subtle defects in vitamin D metabolism, including genetic polymorphisms related to vitamin D, might possibly be involved as well. Optimal 25OHD serum concentrations, throughout the year, may be beneficial for patients with MS, both to obtain immune-mediated suppression of disease activity, and also to decrease disease-related complications, including increased bone resorption, fractures, and muscle weakness.

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Section: Cellular Effectsmentioning

confidence: 84%

Section: Eae and Vitamin D-related Treatmentmentioning

confidence: 99%

Multiple sclerosis and vitamin D: an update

et al. 2004

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“…At the time of death, all mice were experiencing the first attack of EAE and showed spinal cord symptoms typical of the disease such as caudo-cranial ascending paralysis. 12 Cytokines: IL-4 mRNA was 10-fold higher in the spinal cord of IL-4-treated mice (0.92 ± 0.5 AU) compared with control mice (0.05 ± 0.02 AU) (P Ͻ 0.05). IL-1␤ (IL-4-treated mice: 24.6 ± 8.9; control mice: 30.6 ± 12.0 AU) and TNF␣ (IL-4-treated: 73.0 ± 61.6; control mice: 156.8 ± 86.4 AU) did not differ significantly between the two groups.…”

Section: Il-4 Gene Delivery Decreases Spinal Cord Mrna Levels Of Mcp-mentioning

confidence: 98%

“…Immunization was performed in each mouse twice, 7 days apart, as previously described. 12 Mice received 500 ng of pertussis toxin (Sigma, St Louis, MO, USA) i.p. at the time of the immunization and 48 h later.…”

Section: Hsv-1-derived Vectors and Vector Injectionsmentioning

confidence: 99%

Central nervous system gene therapy with interleukin-4 inhibits progression of ongoing relapsing–remitting autoimmune encephalomyelitis in Biozzi AB/H mice

Furlan¹,

Poliani²,

Marconi

et al. 2001

Gene Ther

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Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system (CNS) that might benefit from anti-inflammatory therapies. However, systemic delivery of anti-inflammatory drugs in MS patients has so far been disappointing, mostly due to the limited capacity of these molecules to enter the CNS. We injected into the cisterna magna (i.c.) of Biozzi AB/H mice affected by a relapsing-remitting form of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, a non-replicative herpes simplex virus (HSV) type-1-derived vector containing the interleukin (IL)-4 gene (d120:LacZ:IL-4). CNS delivery of the d120:LacZ:IL-4 vector, after EAE onset, induced the in situ production of IL-4 by CNS-resident cells facing the cerebrospinal fluid (CSF) spaces and reduced by 47% (P Ͻ 0.02) the disease-related deaths. Compared with mice treated with the control d120:LacZ vector, IL-4-treated mice also showed a shorter duration of the first EAE attack, a

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“…If vitamin D3 is used, the beneficial effect predominates in females, likely via a potentiation by oestrogens [Spach and Hayes, 2005;Nashold et al 2009;Subramanian et al 2012]. Various immunological mechanisms have been reported to explain the vitamin D and calcitriol effects: an anti-inflammatory effect [Spach et al, 2004], actions on macrophages [Nashold et al 2000], on different types of cytokines [Cantorna et al 1998;Spach et al 2006;Pedersen et al 2007], on regulatory T lymphocyte cells (Tregs), lymphocyte T helper 1 (Th1), Th17 and Th2 [Mattner et al 2000;Muthian et al 2006;Chang et al 2010;Mayne et al 2011] and invariant natural killer T-cells (iNKTs) [Cantorna et al 2012]. Interestingly, with low VDR gene expression, EAE is facilitated, with an increase in Th1 and Th17, suggesting that, in a similar genetic situation in humans, the MS risk may be increased despite high ambient UV radiation (e.g.…”

Section: Multiplicity Of Vitamin D Actionsmentioning

confidence: 99%

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Pierrot‐Deseilligny

Souberbielle

2013

Ther Adv Neurol Disord

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Abstract:The contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis (MS) is reviewed. Among the multiple recently discovered actions of vitamin D, an immunomodulatory role has been documented in experimental autoimmune encephalomyelitis and in humans. This action in the peripheral immune system is currently the main known mechanism through which vitamin D might influence MS, but other types of actions could be involved within the central nervous system. Furthermore, vitamin D insufficiency is widespread in temperate countries and in patients with MS at the earliest stages of the disease, suggesting that the deleterious effects related to vitamin D insufficiency may be exerted in these patients. In fact, many genetic and environmental risk factors appear to interact and contribute to MS. In genetics, several human leukocyte antigen (HLA) alleles (more particularly HLA-DRB1*1501) could favour the disease whereas some others could be protective. Some of the genes involved in vitamin D metabolism (e.g. CYP27B1) also play a significant role. Furthermore, three environmental risk factors have been identified: past Epstein-Barr virus infection, vitamin D insufficiency and cigarette smoking. Interactions between genetic and environmental risk or protective factors may occur during the mother's pregnancy and could continue during childhood and adolescence and until the disease is triggered in adulthood, therefore possibly modulating the MS risk throughout the first decades of life. Furthermore, some clinical findings already strongly suggest that vitamin D status influences the relapse rate and radiological lesions in patients with MS, although the results of adequately powered randomized clinical trials using vitamin D supplementation have not yet been reported. While awaiting these incontrovertible results, which might be long in coming, patients with MS who are currently in vitamin D insufficiency should be supplemented, at least for their general health status, using moderate doses of the vitamin.

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Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D3

Cited by 218 publications

References 55 publications

Multiple sclerosis and vitamin D: an update

Multiple sclerosis and vitamin D: an update

Central nervous system gene therapy with interleukin-4 inhibits progression of ongoing relapsing–remitting autoimmune encephalomyelitis in Biozzi AB/H mice

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

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