UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production

Abstract

Although the exact cause of multiple sclerosis (MS) is unknown, a number of genetic and environmental factors are thought to influence MS susceptibility. One potential environmental factor is sunlight and the subsequent production of vitamin D. A number of studies have correlated decreased exposure to UV radiation (UVR) and low serum 25-hydroxyvitamin D(3) [25(OH)D(3)] levels with an increased risk for developing MS. Furthermore, both UVR and the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3), suppress disease in the experimental autoimmune encephalomyelitis (EAE) animal model of MS. These observations led to the hypothesis that UVR likely suppresses disease through the increased production of vitamin D. However, UVR can suppress the immune system independent of vitamin D. Therefore, it is unclear whether UVR, vitamin D, or both are necessary for the putative decrease in MS susceptibility. We have probed the ability of UVR to suppress disease in the EAE model of MS and assessed the effect of UVR on serum 25(OH)D(3) and calcium levels. Our results indicate that continuous treatment with UVR dramatically suppresses clinical signs of EAE. Interestingly, disease suppression occurs with only a modest, transient increase in serum 25(OH)D(3) levels. Further analysis demonstrated that the levels of 25(OH)D(3) obtained upon UVR treatment were insufficient to suppress EAE independent of UVR treatment. These results suggest that UVR is likely suppressing disease independent of vitamin D production, and that vitamin D supplementation alone may not replace the ability of sunlight to reduce MS susceptibility.

Fig. 1.

UVB pretreatment fails to suppress EAE and causes a slight increase in serum 25(OH)D₃ levels. Mice were treated for 7 days before immunization with the indicated doses of UVB. (A) Average clinical EAE scores were determined daily for control and UVB treated mice (n = 7–12). (B) Mice were weighed weekly (±SD) throughout the study to monitor disease-associated weight loss and toxicity. (C) Serum calcium levels (±SD) were determined at the end of the experiment using a clinical chemistry analyzer. (D) Serum 25(OH)D₃ levels (±SD) were determined at the end of UV treatment and at the termination of the experiment.

Fig. 2.

Continuous UVB treatment suppresses EAE and causes a transient increase in serum 25(OH)D₃ levels. After immunization, mice were treated either every other or every third day with 2.5 kJ/m² UVB. (A) Average clinical EAE scores were determined daily for control and UVB treated mice (n = 10–11). (B) Mice were weighed weekly (±SD) throughout the study to monitor disease-associated weight loss and toxicity. (C) Serum calcium levels (±SD) were determined at the end of the experiment using a clinical chemistry analyzer. (D) Serum 25(OH)D₃ levels (±SD) were determined at selected time-point throughout the experiment. *, P < 0.05 compared to control group.

Fig. 3.

25(OH)D₃ only modestly suppresses EAE at doses that cause severe hypercalcemia. Beginning 10 days before immunization, mice were fed a purified 0.87% calcium diet delivering the indicated doses of either 25(OH)D₃ or 1,25(OH)₂D₃. Treatment continued for the duration of the experiment. (A) Average clinical EAE scores were determined daily for vehicle, 25(OH)D₃-, and 1,25(OH)₂D₃-treated mice (n = 15–17). (B) Mice were weighed weekly (±SD) throughout the study to monitor weight loss and toxicity. (C) Serum calcium levels (± SD) were determined at the end of the experiment using a clinical chemistry analyzer. (D) Serum 25(OH)D₃ levels (±SD) were determined at the termination of the experiment. *, P < 0.05 compared with control group.