Hepatitis B Virus Researchers Make Important Discovery in the Field of Immunology

[sorte]

http://hepatitisnewstoday.com/2015/05/19/hepatitis-b-virus-researchers-make-important-discovery-field-immunology/

This week, a group of interdisciplinary researchers from the University College London (UCL) released study findings in which they made a discovery that could have important implications in several clinical disciplines. The study entitled, “Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells,” focused on the reasons why the immune system cannot control hepatitis B virus (HBV) infection once it becomes established in the liver, and the findings could potentially lead to new therapeutic drug targets to treat HBV infections. The study was published in the latest edition of Nature: Medicine....

[mike9111]

Although sounds interesting i start to put doubt in all of this. It seems they just want money and they start predict all the good news and wheb they receive their money theb they comeback and saybit failed

[stef2011]

oh my...cut off food supply of immune system...wht is this mickey mouse newspaper.....
anyway maybe nature article is better and i have not read it but i dont see any great discovery here...we already know what to use to activate cd8, anti pdl1 drugs

[studyforhope]

Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells.
Pallett LJ1, Gill US2, Quaglia A3, Sinclair LV4, Jover-Cobos M5, Schurich A1, Singh KP1, Thomas N1, Das A1, Chen A1, Fusai G5, Bertoletti A6, Cantrell DA4, Kennedy PT2, Davies NA5, Haniffa M7, Maini MK1.
Author information

Abstract
Infection with hepatitis B virus (HBV) results in disparate degrees of tissue injury: the virus can either replicate without pathological consequences or trigger immune-mediated necroinflammatory liver damage. We investigated the potential for myeloid-derived suppressor cells (MDSCs) to suppress T cell-mediated immunopathology in this setting. Granulocytic MDSCs (gMDSCs) expanded transiently in acute resolving HBV, decreasing in frequency prior to peak hepatic injury. In persistent infection, arginase-expressing gMDSCs (and circulating arginase) increased most in disease phases characterized by HBV replication without immunopathology, whilst L-arginine decreased. gMDSCs expressed liver-homing chemokine receptors and accumulated in the liver, their expansion supported by hepatic stellate cells. We provide in vitro and ex vivo evidence that gMDSCs potently inhibited T cells in a partially arginase-dependent manner. L-arginine-deprived T cells upregulated system L amino acid transporters to increase uptake of essential nutrients and attempt metabolic reprogramming. These data demonstrate the capacity of expanded arginase-expressing gMDSCs to regulate liver immunopathology in HBV infection.

[studyforhope]

one wonders if orally supplied l arginine might help to activate these t cells.

[stef2011]

has carnitine anything to do with this scenario or with arginine?

i remember that a trial of adv plus peg found lowest carnitine levels on those with hbsag loss
http://www.ncbi.nlm.nih.gov/pubmed/24824278

[stef2011]

dont know if this has anything to do with our situation.we may try although it sounds to easy to reverse cd8 to full activity by simply taking arginine

http://www.jbc.org/content/277/24/21123.full.html

In addition, the work presented here suggests that the CD3ζ down-regulation induced by L-Arg starvation is not caused by apoptosis but rather through post-transcriptional mechanisms that decrease the half-life of the CD3ζ mRNA. This process is completely reversible by the replenishment of L-Arg.

[stef2011]

http://www.bloodjournal.org/content/109/4/1568?sso-checked=true

l-arginine availability regulates T-lymphocyte cell-cycle progression


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519282/

Metabolism of L-Arginine by Myeloid-Derived Suppressor Cells in Cancer: Mechanisms of T cell suppression and Therapeutic Perspectives

[studyforhope]

I also doubt that supplemental arginine can completely restore T cell function, but it might help substantially to improve it. It is well known that nitric oxide in the liver acts as a critical hbv suppressing agent and it is likely also involved in T cell activation mechanisms beyond that. Thus addition of 4 times a gram of oral  l arginine per day might well speed up immune elimination mechanisms.

I don't know about a relationship of arginine to carnitine metabolism.

[stef2011]

http://jn.nutrition.org/content/137/6/1681S.full.pdf+html

[sorte]

so maybe l-arginine may be another interesting supplement

[NewlyDiscovered]

Any particular brand of l-argunine to try? I looked up iherb and saw mainly muscle building supplements.

Thanks

[stef2011]

choose the ones without magnesium stearate, it can give issues with absorption of other vitamins and supplements

for now i found nowfoods powder with no addittives or pills at 1g with few addittives

[stef2011]

in europe i found nowfoods at luxebc.com

[stef2011]

http://www.luxebc.com/supplements-c394/amino-acids-c549/l-arginine-c552/l-arginine-powder-1-kg-2-2-lbs-p16348

http://www.luxebc.com/supplements-c394/amino-acids-c549/l-arginine-c552/l-arginine-powder-1-lb-454-g-p15732

quite expensive....but i got it i dont eat a lot of meat, fish and no dairies, so i guess i am deficient of this anyway in my diet

now we have to look for safe max dose

[NewlyDiscovered]

Thanks Stef.

Seems a lot cheaper here

http://m.iherb.com/Now-Foods-Sports-L-Arginine-Powder-1-lb-454-g/369

[stef2011]

thanks but iherbs is not in europe, there are custom charges and delays

please check if there is any supplementation study, i read some yesterday and it looks like 3g/day or 30g day dont remember

[stef2011]

http://www.drugs.com/npp/l-arginine.html

it says 30g/day here, on a very fast read it looks like it has no tox or sides

[stef2011]

http://bigvits.co.uk/product.php?pid=186

this is the cheapest website i found in europe, nowfoods, no magnesium stearate, pure powder

[Royal36]

I found here in my area the L-Argnine 500mg which has a magnesium citrate on it & on the bottle it says i can take from 1-6 tablets in a day, just to give a try i started with two which is 1000mg a day it means but it has a terrible headache side effect. Is this normal or it is due to my f2-f3 fibrosis level my liver reacting to the tablet? Appreciate!

[stef2011]

dont know about magnesium citrate, best use pure powder form

the problem with magnesium stearate is that it is used to move substances easily without loss when making vitamins but in our gut it interferes with absorption of nutrients

[Royal36]

Apologize citrate can be corrected as stearate.

[Royal36]

So stif is there any interaction of L-Argnine 500mg with the Nuc's like entecavir?

[stef2011]

no this is just a try to see if arginine can improve t cell function, i think we can see more from patients on peginterferon, pegintf+nucs and even when peg is finished if there was response...on nucs alone i think it is difficult to see any effect but nothing to low and no harm from this

magnesium stearate is bad, choose supplements without it in the future

[stef2011]

started today adding arginine powder, i took a single dose about 18.4g (doses used from 4 to 30g on trials)...some diarrhea so probably best small doses during the day