UV light suppression of EAE (a mouse model of multiple sclerosis) is independent of vitamin D and its receptor.

Vitamin D and sunlight have each been reported to protect against the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). To date, the contribution of each has been unclear as ultra violet (UV) exposure also causes the generation of vitamin D in the skin. To examine whether the UV based suppression of EAE results, at least, in part from the production of vitamin D, we studied the effect of UV light on EAE in mice unable to produce 7-dehydroxycholesterol (7-DHC), the required precursor of vitamin D. Furthermore, we examined UV suppression of EAE in mice devoid of the vitamin D receptor (VDR). Our results demonstrate that UV light suppression of EAE occurs in the absence of vitamin D production and in the absence of VDR. Future investigations will focus on identifying the pathway responsible for the protective action of UV in EAE and presumably human MS.

Salate derivatives found in sunscreens block experimental autoimmune encephalomyelitis in mice.

UV light suppresses experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, in mice and may be responsible for the decreased incidence of MS in equatorial regions. To test this concept further, we applied commercially available sunblock preparations to mice before exposing them to UV radiation. Surprisingly, some of the sunblock preparations blocked EAE without UV radiation. Furthermore, various sunblock preparations had variable ability to suppress EAE. By examining the components of the most effective agents, we identified homosalate and octisalate as the components responsible for suppressing EAE. Thus, salates may be useful in stopping the progression of MS, and may provide new insight into mechanisms of controlling autoimmune disease.

Suppression of experimental autoimmune encephalomyelitis by ultraviolet light is not mediated by isomerization of urocanic acid.

BACKGROUND: Ultraviolet B irradiation confers strong resistance against experimental autoimmune encephalomyelitis, a model of multiple sclerosis. This protection by ultraviolet B is independent of vitamin D production but causes isomerization of urocanic acid, a naturally occurring immunosuppressant. METHODS: To determine whether UCA isomerization from trans to cis is responsible for the protection against experimental autoimmune encephalomyelitis afforded by ultraviolet B, trans- or cis-urocanic acid was administered to animals and their disease progression was monitored. RESULTS: Disease incidence was reduced by 74% in animals exposed to ultraviolet B, and skin cis-urocanic acid levels increased greater than 30%. However, increasing skin cis-urocanic acid levels independent of ultraviolet B was unable to alter disease onset or progression. CONCLUSIONS: It is unlikely that urocanic acid isomerization is responsible for the ultraviolet B-mediated suppression of experimental autoimmune encephalomyelitis. Additional work is needed to investigate alternative mechanisms by which UVB suppresses disease.

UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). The incidence of MS is inversely related to sun light exposure or ultraviolet radiation (UVR). UVR was found to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of MS, independent of vitamin D production. The mechanism of this suppression remains to be elucidated. To this end, several elements of an immune response in the spinal cord, spleen and skin during development of EAE were studied. As expected, UVR (10kJ/m(2)) inhibits inflammation and demyelination of the spinal cord. Most significant, UVR dramatically reduced spinal cord chemokine CCL5 mRNA and protein levels. UVR also suppressed IL-10 in skin and spleen but not the spinal cord. As expected from the UVR action on skin, macrophage population and IFN-γ levels are increased in that organ. UVR had no effect on lymphocyte proliferation and IFN-γ in spleen. From these measurements, we suggest that UVR suppression of EAE prevents the migration of inflammatory cells into the CNS by a focal inhibition of chemokine CCL-5 in the CNS and a systemic elevation of immunosuppressive IL-10.

Development of experimental autoimmune encephalomyelitis (EAE) in mice requires vitamin D and the vitamin D receptor.

The development of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, has been studied in mice that were (i) vitamin D-deficient, (ii) minus the vitamin D receptor, (iii) minus a vitamin D 25-hydroxylase, and (iv) minus the vitamin D 25-hydroxyvitamin D-1α-hydroxylase. EAE development was markedly suppressed in mice lacking the vitamin D receptor and partially suppressed in vitamin D-insufficient mice. However, the absence of either of the two key hydroxylases (i.e., 25-hydroxylase and 1α-hydroxylase) neither inhibits nor enhances the development of EAE. These results indicate that vitamin D and the vitamin D receptor are required for the development of EAE. The results also suggest that 1,25-dihydroxyvitamin D(3) may not play a role in this autoimmune response.

Suppression of experimental autoimmune encephalomyelitis by 300-315nm ultraviolet light.

Multiple sclerosis (MS) is a chronic debilitating disease, with lowest incidence in equatorial regions and highest incidence in temperate regions. This relationship is believed to be related to sunlight or UV light exposure. Recent evidence with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, established that this suppression is not mediated by vitamin D production. UV is comprised of three general wave bands: UVC (100-280nm), UVB (280-320nm) and UVA (320-400nm). In the present study we used four lamps that emit different wavelengths of UV: (1) broad band UVB (BB-UVB: 280-320nm); (2) narrow band UVB (NB-UVB: 300-315nm); (3) broad band UVA (BB-UVA: 300-400nm); and (4) long wavelength UVA (UVA-1: 340-400nm). The effect of these light sources was studied in vitamin D-sufficient C57BL/6 mice. The NB-UVB largely accounted for the suppression and delay of onset of EAE by BB-UVB. In contrast, UVA-1 failed to suppress EAE severity at low (∼2.5KJ/m(2)), medium (∼5.0KJ/m(2)) and high (∼10.0KJ/m(2)) doses. Serum calcium and 25-(OH)D3 levels were unchanged after both NB-UVB and UVA-1 treatments. The results demonstrate that NB-UVB (300-315nm) is largely responsible for light-induced suppression of EAE and its effect is not via production of vitamin D.