The effect of vitamin D supplementation on the gene expression of See-Saw model interleukines in the first degree of apparently healthy relatives of multiple sclerosis patients.

Abstract

Background: Our main aim was to assess the effects of dietary vitamin D3 on proinflammatory (IL -17A & IL-6) and anti-inflammatory (IL-10) cytokines. In the present study, we have proposed a schematic model for the fluctuation of pro- and anti-inflammatory cytokines by vitamin D3, referred to as the See-Saw model. In fact, we assessed balance and stabilization of this model in MS patients compared to two control groups. Method: Our clinical trial study was conducted on 75 participants with ages between 30±10 which divided in three groups by simple random sampling: Multiple Sclerosis Participants (MSP, n=25, male=4, female=21), First-Degree Relative Participants (FDRP, n=25, male=8, female=17), and Healthy Participants (HP, n=25, male=5, female=20). All groups received 50000 IU vitamin D3/week for 8 weeks. Serum 25-(OH) vitamin D3 levels and mRNA expression levels of interleukins were determined using Electro Chemiluminescence (ECL) assay and Real-Time PCR, respectively. Results: In before supplementation, vitamin D difficiecy in MSP, FDRP and HP was 68%, 80% and 80%, respectively; so that, after supplementation, these amounts reduced to 12%, 16% and 20%, respectively. Vitamin D3 affected the levels of IL-17A, IL-10, and IL-6 among the three groups (P<0.001). Levels of IL-17A (MSP: fold change (FC) = 5.9, P=0.014; FDRP: FC = 5.2, P=0.006; HP: FC = 4.2, P=0.012) and IL-6 (MSP: FC = 5.6, P=0.003; FDRP: FC = 5.5, P=0.002; HP: FC = 5.1, P <0.001) were down-regulated following vitamin D3 treatment. In addition, levels of IL-10 (MSP: FC = 6.2, P=0.005; FDRP: FC = 4.6, P<0.001; HP: FC = 5.2, P<0.001) were up-regulated after 8 weeks. Conclusion: Supplementation with vitamin D3 reduced the mRNA expression levels of IL-17A and IL-6, and it increased the mRNA expression level of IL-10 in all groups. However, these effects were more remarkable in the MSP group than in the other groups. Interestingly, in a deficiency state of serum vitamin D3, IL-17A the other groups. Interestingly, in a deficiency state of serum vitamin D3, IL-17A expression had a positive feedback effect on the expression of IL-6. Conversely, in the sufficient state, IL-10 expression had a negative feedback effect on the expression of IL-17A and IL-6.