I am totally confused about the role IL-17 plays in MS. #ImmunologySpeak #MSBlog #MSResearch
"The following study on the effect of high-dose vitamin D supplementation on immune function is difficult to interpret. They have focused on one molecule, or cytokine (immune messenger), called IL-17 that is involved in T-cell autoimmunity. Firstly, I am not sure what form of IL-17 was being measured? I assume IL-17A. In addition to IL-17A, the IL-17 family includes IL-17B, IL-17C, IL-17D, IL-17E (also called IL-25), and IL-17F. They show that there is no change in levels between baseline and 12 weeks in both the group of MSers given high-dose vD and the group who did not receive vD. Despite not signficant change in serum levels across the groups they then provide an analysis then the consumption of vD was positively associated with serum IL-17 levels with R2=0.91; in other words 91% of the variance of IL-17 levels can be explained by the consumption of vD. I would be interested to see the scatter plot of the data; with a R, or correlation coefficient of 0.95 (95%), it should be straight line. Unfortunately, there is no graph in the paper to look at."
"In terms of the biological meaning of this data I haven't a clue. In other studies vD has been shown to reduce the production of IL-17 from immune cells and have little effect on serum IL-17 levels. These results are counterintuitive and will need to reproduced and linked to other markers of immune activation and disease activity."
"This study is typical of most MS immunology studies; it asks more questions than it answers, it doesn't support the current dogma and contradicts other published data in the literature. This is why I haven't a clue about the role of IL-17 in MS; let's hope the new trial of a monoclonal antibody that inhibits IL-17 will answer the question for us."
Toghianifar et al. Effect of high dose vitamin D intake on interleukin-17 levels in multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial. J Neuroimmunol. 2015; 285:125-8.
BACKGROUND: Vitamin D has immunomodulatory effects in multiple sclerosis (MS). Vitamin D acts through various mechanisms such as secretion of cytokines. Interleukin-17 (IL-17) is a critical interleukin in inflammatory response in MS.
OBJECTIVE: This study assessed the effect of oral high dose vitamin D intake on IL-17 levels in MS patients in a double blind randomized clinical trial.
METHODS: 94 patients with a diagnosis of relapsing remitting multiple sclerosis (RRMS) were randomized to two groups. One group received 50,000 IU vitamin D3 every five days for 12 weeks. The other group was given placebo. Both groups received interferon-β (IFN-β) treatment. Serum levels of IL-17 were measured at the beginning of the study and after 12 weeks.
RESULTS: IL-17 serum levels were 56.75±28.72pg/ml and 30.31±75.85pg/ml in the intervention and placebo group at the beginning of the study, respectively (Median±IQR, p=0.338). After 12 weeks, IL-17 levels were 58.93±67.93pg/ml and 46.13±94.70pg/ml in the intervention and placebo group, respectively (Median±IQR, p=0.960). The multiple linear regression analysis indicated that the consumption of vitamin D3 was positively and significantly associated with the logarithm of IL-17 measures (β=1.719; p=0.002 and R2=0.91), adjusted by EDSS scores.
CONCLUSION: IL-17 levels showed significant change in RRMS patients after receiving high dose vitamin D3 for 12 weeks.