Sunday, 26 July 2015

ImmunologySpeak: IL-17 and vitamin D

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."



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.

9 comments:

  1. High levels of vit D3 is linked to strokes, Prof G.

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    1. Yes we know the publication you are taking about,but it is not always clear cut here are some papers in the last few months,

      Park KY et al. Serum Vitamin D Status as a Predictor of Prognosis in Patients with Acute Ischemic Stroke.Cerebrovasc Dis. 2015 Jul 11;40(1-2):73-80. Serum 25(OH)D levels in patients with good outcomes were significantly higher than those with poor outcome (50.2 ± 32.7 vs. 43.9 ± 30.0 nmol/l, p = 0.007).

      Thiele I,et al. Atherosclerosis. 2015; 241:743-51.
      Supplementation of calcium (Ca) and vitamin D for the prevention of osteoporosis is frequently found in Western countries. Recent re-analyses of clinical trials observed a higher risk of myocardial infarction and stroke in subjects taking Ca (+vitamin D)
      supplements

      Low Serum Vitamin D Is Independently Associated with Larger Lesion Volumes after Ischemic Stroke. Turetsky A, Goddeau RP Jr, Henninger N.
      J Stroke Cerebrovasc Dis. 2015;24(7):1555-63.

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    2. It really is not clear cut as MD states. Unless you have a really -really - terrible diet or a health condition that makes calcium hard to absorb or take a medication that leeches it from your body, you *should* be getting enough calcium without needing to supplement. Though it's worth finding out what your calcium levels are - your GP can order this test (with any vitamin/mineral supplement, it's best to establish a baseline before you start, otherwise, you could be wasting your money/not getting the correct dosage;and getting a good supplement is another story entirely). Where possible I use food not supplements but D3 is far harder to obtain, especially as one gets older and also the darker your skin is - so a supplement is a very good idea.

      Note the study referred to above says Calcium plus Vitamin D -this is where the not clear cut comes in. Vitamin D increases absorption of Calcium from food sources, sometimes substantially, so why supplement calcium on top? Of course this may lead to a greater risk of stroke. Chances of having a stroke: in my case pretty darn low. Chances of having an MS relapse: much higher.

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  2. "with a R, or correlation coefficient of 0.95 (95%), it should be straight line."

    The R^2 value has nothing to do with the linearity of the data, it's easy to construct cases in which the data are essentially noise but there's a high R^2. Also, they reported the results of regressing the log IL-17 values, not raw IL-17 values. R^2 isn't preserved under non-linear transformations, so we don't know anything about the relationship between IL-17 and vitamin D.

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    1. Are you a boffin, sir?

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    2. https://en.wikipedia.org/wiki/Coefficient_of_determination

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    3. MD: was the link a response to the initial comment on this thread?

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    4. I posted it because I had a look at r2/R2. as to your former comments.

      You were questioning ProfG and so he can answer your comments or not

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  3. I don't know how god the statistics was in this paper - but the medians mentioned in the abstract do not suggest any correlation of vit D with IL17 - median IL17 did not change at 12 weeks in the intervention group (56.7 vs, 58.9), but it did change somewhat in the placebo group (30.3 vs. 46.1). The real problem is standard deviations, which exceed median IL17 values.

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