Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1 α, 25-(OH)2D3

doi:10.1016/0165-5728(95)00076-E

Journal of Neuroimmunology

Volume 61, Issue 2, September 1995, Pages 151-160

https://doi.org/10.1016/0165-5728(95)00076-E Get rights and content

Abstract

The hormone 1 α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) has immune modulatory activities in vitro and in vivo, and can prevent or delay the onset of experimental or spontaneous autoimmune diseases. At therapeutical doses, however, hypercalcemic side effects are found. The present experiments examined the effects of combined treatment with subtherapeutic doses of cyclosporine A (CsA) and 1,25(OH)₂D₃ on the evolution of experimental autoimmune encephalomyelitis (EAE) in SJL mice. 1,25(OH)₂D₃ at 5 μg/kg body weight (given by i.p. injection every 2 days) prevented the appearance of paralysis in 70% of the treated mice. The treatment with 1,25(OH)₂D₃ at 2 μg/kg/2 days alone had less substantial protective effects (22% disease-free animals versus 5% in the control group). However, when this subtherapeutic dose was associated to treatment with a daily dose of CsA (2 or 5 mg/kg/day), which by itself was subtherapeutic (24 and 50% disease-free animals, respectively), the association of both drugs led to near-total protection (86% disease-free animals when combined with the highest dose of CsA). When an alternate day administration schedule (CsA at 10 mg/kg and 1,25(OH)₂D₃ at 2 μg/kg, each given on alternate days from day −3 to +19 after disease induction) was used, all treated mice were completely protected clinically and histologically. The two drugs also showed additive effects on serum osteocalcin and urinary calcium and desoxypyridinoline excretion, but not on serum calcium concentration. Our experiments demonstrate that 1,25(OH)₂D₃ might be a potential dose-reducing agent for CsA in immunosuppressive therapy.

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Citation Excerpt :
Although vitamin D's primary role is in maintaining calcium homeostasis, a role for vitamin D in immune regulation is supported by several lines of evidence [77]. In animal models, calcitriol 1,25(OH)2D has been shown to protect against the development and progression of experimental autoimmune encephalomyelitis (EAE) [78–83]. It appears that this effect is mediated through promotion of regulatory T-cell function as opposed to direct effects on Th1 or Th2 cells [77,84].
Multiple sclerosis (MS) is a relatively common debilitating neurologic disease that affects people in early adulthood. While the characteristic pathology of MS has been well described, the etiology of the disease is not well understood, despite decades of research and the identification of strong genetic and environmental candidates for susceptibility. A question central to all diseases, but posed specifically for MS at the XVI European Charcot Foundation Lecture, was ‘Can MS be prevented?’ To address this question, we have evaluated the available data regarding nutritional and environmental factors that may be related to MS susceptibility and suggest the extent to which a potential intervention may reduce disease burden. It is our opinion that intervention, particularly supplementation with vitamin D, could have a dramatic impact on disease prevalence. Understanding that any intervention or behavioral modification will surely act in the context of genetic susceptibility and unidentified stochastic events, it is likely that not all MS is ‘preventable’. Epidemiologic observation has provided key insights into environmental and nutritional factors that may alter one's susceptibility to MS, however, there are still many questions in unraveling the etiology of this complex disease.

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Research paperPrevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1 α, 25-(OH)2D3

Abstract

Steroids

Cell. Immunol.

Biochem. Pharmacol.

J. Neurol. Sci.

Lancet

Clin. Immunol. Immunopathol.

Cell. Immunol.

Cell. Immunol.

Metabolism

Cell. Immunol.

Steroids

Biochem. Biophys. Res. Commun.

Immunol. Today

J. Biol. Chem.

Cell. Immunol.

Immunol. Lett.

Immunopharmacology

Blood

Semin. Arthr. Rheum.

Bone

Prevention of immunological disorders in MRL/1 mice by a new synthetic analogue of vitamin D3: 22-oxa-1α,25-dihydroxyvitamin D3

J. Nutr. Sci. Vitaminol.

Regulation of interleukin-1 and tumour necrosis factor gene expression in myelomonocytic cell lines by 1,25-dihydroxyvitamin D3

Immunology

Pharmacology of cyclosporine (Sandimmune). Pharmacological properties in vitro

Pharmacol. Rev.

Structure-function relationships in the vitamin D endocrine system

Endocrinol. Rev.

Partial prevention of active Hey mann nephritis by 1α,25 dihydroxyvitamin D3

Clin. Exp. Immunol.

Relapsing experimental allergic encephalomyelitis in the SJL/J mouse

Lab. Invest.

Effects of cyclosporin A on expression of IL-2 and IL-2 receptors in normal and multiple sclerosis patients

Clin. Exp. Immunol.

Pharmacology of cyclosporine (Sandimmune). Pharmacological effects on immune function: in vitro studies

Pharmacol. Rev.

Patterns of blood-brain barrier breakdown in inflammatory demyelination

Brain

Research paper
Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1 α, 25-(OH)₂D₃

Prevention of immunological disorders in MRL/1 mice by a new synthetic analogue of vitamin D₃: 22-oxa-1α,25-dihydroxyvitamin D₃

Regulation of interleukin-1 and tumour necrosis factor gene expression in myelomonocytic cell lines by 1,25-dihydroxyvitamin D₃

Partial prevention of active Hey mann nephritis by 1α,25 dihydroxyvitamin D₃