Tuesday, 12 March 2013

Research: too much salt is bad for you if you are a mouse with EAE

#MSBlog: What does too much salt do to MS?

First  question it was asked the on the Nature site & removed. 
What is the relevance of the animal data because if you look at the equivalent dose used in the mice to translate from animals to humans, they need to eat/drink 600g salt a day. Compare this to the average human daily consumption of about 6g a day.

EpubKleinewietfeld et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013 Mar 6. doi: 10.1038/nature11868.


Placebo tablets are often salt tablets, however, new research suggests that salt may influence the immune response.

 Kleinewietfeld et al. and Wu et al. provide evidence that a high-salt diet can enhance the differentiation of a class of immune cells called TH17 cells, which can exacerbate disease in a mouse model of MS called experimental autoimmune encephalitis (EAE). They also show that mice whose T cells lack the enzyme SGK1 (T-cell SGK−/−) display reduced disease severity and are protected from salt-exacerbated EAE.

The authors demonstrate that salt concentration outside cells and signalling through the IL-23 receptor (cell surface molecules) both influence the activity of SGK1 to drive expression of disease-causing TH17-cells, which include the production of the cytokines (mesages that cells use to communicate with each other) IL-17A and IL-17F and enhanced expression of the IL-23 receptor (IL-23R) and the transcription factor RORĪ³T (encoded by Rorc). Transcription factors are essentially factors that move from the cell into the nucleus to turn on, or off, the expression of genes. However, this finding must be considered in the context of other environmental factors, such as oxygen and nutrient provision. These influence signalling pathways and glucose metabolism in ways that regulate not only TH17-cell differentiation, but also that of other classes of T cells.



"What is the evidence that high salt diet has an effect on human autoimmune disease(s)? I am not aware of any. Should we ignore this study? No we should not! We should probably explore whether or not salt intake is in any way linked to MS disease susceptibility or disease course (prognosis). I will need to speak to my epidemiology colleagues about the feasibility of this study. May be this sort of data is being collected in other studies and the question can be asked from existing data sets. Any suggestions or insights?"

This study indicates that high salt concentrations induce a Th17 response and augment autoimmunity. There was no dose-response and so we don't know if a low salt diet was protective.

5 comments:

  1. Hmmm, problem is that the control EAE is rubbish and high salt diet merely makes it more like what you would expect. Possibly a little bias on the scoring?
    I take these results with a pinch of salt (I'll get me coat................)!

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  2. Also the diet had 4% salt and the water 1% salt. I suspect these levels are much higher than a human might be expected to consume. Perhaps a nutritionist might care to comment?

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    1. MD2 - does the finding has nothing to do with you testing sodium channel blockers in nerves? I know salt is a different sodium but the theory that too much sodium damages nerves could make sense, no? Also salt has been proven to negatively impact on a host of different diseases. Also maybe the EAE is flawed but not the theory per se?

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    2. The findings relate to cells of the immune system and not to the function of sodium channels in nerves. It is the upregulation of sodium channels on demyelinated nerves that may contribute to neuronal degeneration not high sodium levels per se. Blocking of these cannels seems to be neuroprotective in our mouse model. A clinical trial to investigate this is now starting under the auspices of Prof G.
      As you say the EAE results may be a little iffy but the theory may have some legs. It's difficult on reading the paper to get a handle on how the high salt diet the mice were consuming relates to the human situation.

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  3. I've just been doing some back of an envelope calculations and deduce for the typical amount of food and water a mouse consumes a day and the salt content used in the experiment for this to be extrapolated to a 70 kg human you would need to consume half a kilo of salt per day! Indicating that you would be long dead well before you developed MS!

    I suggest it's back to the drawing board with this!

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