Low Intereferon alpha in CFS - linked to CNS inflammation?

natasa778

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I wonder if one possible explanation for low levels in blood could be high levels in the brain - NEURONS AND GLIAL CELLS (and even cerebrospinal fluid?) - have those been measued in CFS?? and also in/around endothelial tissue, and similar hiding places for xmrv.

This is odd but is the case for example with TNF-alpha in autism - very high levels in brain and CFS, but low levels in the blood. Again with interferon alpha, high levels in CFS and brain, no data (?) on blood levels.

Anyone know enough about IFN alpha to comment? Could this be the case of molecules that are produced locally in infected tissue, and therefore not circulating in the blood? Or something like that. So low blood levels are a consequence of some sort of IFN alpha "homeosasis" (this is now known to be the case with many neurotransmitters for example - there is one study showing low blood levels of one particular neurtransmitter actually reflected high levels in the brain, and researches then managed to reduce brain levels by raising blood levels via intravenous supplementation)

here are some interesting indications: http://www.jstor.org/stable/30112028?seq=1
(cytokine levels in serum and CSF of patients with CFS)

Cytokines and the Brain (great info on IFN alpha effects on brain function and CFS symptoms) http://www.psych.illinois.edu/~eroy/396er/cytokines.pdf
 

ukxmrv

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Hi Natasha,

Probably not much good to you but I thought that I would toss it in. I am XMRV+ and my TNF-a has always been high on tests. I am going to take a look when I can get out of bed and see what my IF/a was like. As I remember it was only shown as a ratio on the test results page I got. My doctor spoke about If/a in that consultataion and I took some notes. Currently bedbound but I'll add it when I can.
 
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Gerwyn

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Hi Natasha,

Probably not much good to you but I thought that I would toss it in. I am XMRV+ and my TNF-a has always been high on tests. I am going to take a look when I can get out of bed and see what my IF/a was like. As I remember it was only shown as a ratio on the test results page I got. My doctor spoke about If/a in that consultataion and I took some notes. Currently bedbound but I'll add it when I can.
hi natasa i,ve posted on the other thread I dont know hoe totransfer .Do you want me to repost?
 
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Gerwyn

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inf alpha and beta gene stimulation/regulation and creb involvement

nterferon Regulatory Factor 3 and CREB-Binding Protein/p300 Are Subunits of Double-Stranded RNA-Activated Transcription Factor DRAF1
Brian K. Weaver,1,2 K. Prasanna Kumar,2 and Nancy C. Reich2,*

Graduate Program in Molecular and Cellular Biology1 and Department of Pathology,2 State University of New York at Stony Brook, Stony Brook, New York 11794

Received 20 June 1997/Returned for modification 13 August 1997/Accepted 10 December 1997

Cells respond to viral infection or double-stranded RNA with the transcriptional induction of a subset of alpha/beta interferon-stimulated genes by a pathway distinct from the interferon signal pathway.

All that means that there is more than one way that interferons are produced in response to a viral infection


The transcriptional induction is mediated through a DNA sequence containing the alpha/beta interferon-stimulated response element (ISRE).

production of interferon alpha and beta is switched on by isre like a mini gene or a molecular dimmer switch which emitts a signal



We previously identified a novel transcription factor, designated double-stranded RNA-activated factor 1 (DRAF1), that recognizes this response element.

draf recognises the signal emitted by the dimmer switch


The DNA-binding specificity of DRAF1 correlates with transcriptional induction, thereby distinguishing it as a positive regulator of alpha/beta interferon-stimulated genes.

draf turns the dimmer switch up or down


Two of the components of DRAF1 have now been identified as interferon regulatory factor 3 (IRF-3) and the transcriptional coactivator CREB-binding protein (CBP)/p300.

draf which regulates how much interferon is made is made up of two proteins IF-3 which we dont need to bother with and CREB binding protein made by the CREB gene that XMRV binds inside




We demonstrate that IRF-3 preexists in the cytoplasm of uninfected cells and translocates to the nucleus following viral infection. Translocation of IRF-3 is accompanied by an increase in serine and threonine phosphorylation. Coimmunoprecipitation analyses of endogenous proteins demonstrate an association of IRF-3 with the transcriptional coactivators CBP and p300 only subsequent to infection.

The Creb gene only gets involved after the the viral infection is underway

In addition, antibodies to the IRF-3, CBP, and p300 molecules react with DRAF1 bound to the ISRE target site of induced genes.

The cellular response that leads to DRAF1 activation and specific gene expression may serve to increase host survival during viral infection.

If the CREB gene is not producing a protein of the right shape(possibly due to xmrv integration) then the person is much more prone to the effects of other viral infections.The symptoms would be a lot more severe than normal.

An enterovirus for example could lead to an outbreak of nasty abnormal symptoms
 

Doogle

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When I was at my sickest my alpha interferon was sky high and when I was much better on Ampligen my alpha interferon blood levels went to non detectable.
 
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Gerwyn

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raised interferon levels occur in almost all patients with functional virally induced functional encephalopathy

The new name for our condition is Myalgic encephalopathy

Developmental Medicine & Child Neurology (2006), 48:4:294-300 Mac Keith Press
Copyright 2006 Mac Keith Press
doi:10.1017/S0012162206000636

Original Articles
Childhood encephalopathy: viruses, immune response, and outcome
Michael Clarke a1, Richard W Newton a2 c1, Paul E Klapper a3, H Sutcliffe a4, I Laing a5 and Geoff Wallace a6
 

ramakentesh

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How did you get your TNF alpha levels checked? i have Ankylosing Spondyilits yet ive never had my tnf alpha levels checked - my doc said that tnf serum levels were 'meaningless'
 

JillBohr

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Just wanted to jump in here. I have been wondering about the interpheron alpha and the levels of it in autism. As I was watching my son last night, I decided to read up on some papers Dr. Goldberg wrote many years ago. I noticed that on his tests that he recommends for his patients is the Alpha Interferon test. We should ask some of the NIDS parents what their levels are. Anyway, here is a link to what he wrote about alpha interferon.

http://www.neuroimmunedr.com/Articles/Autism___PDD/immuneconnection.pdf

Also at the Las Vegas conference, Dr. E. Gene Stubbs hypothesized that interferon alpha (INF), a product of many cells, but especially cells of the immune system, may be a major factor in the cause of autism. When INF is given in large doses to children with cancer, the result is that they withdraw and become noncommunicative. These are primary symptoms of autism. Also, children with autism have higher pain thresholds, and elevated endorphins in their cerebral spinal fluid. INF can activate endorphin receptors and is a potent analgesic. In addition, INF has been reported to contribute to autoimmune disorders and allergies. An increased incidence of antinuclear antibodies has also been reported in these children. Children with autism frequently have an impaired immune function: high levels of INF could impair the immune function.
Naturally, this confuses me because they are talking about higher levels of INF but this does look like they are looking in the CFS not peripheral blood. As I read further...

In a preliminary study, 10 autistic children were tested for their level of serum INF. All 10 children with autism had a higher incidence of serum INF than the control adults. Normally, levels of INF are not detectable unless one had an infectious disease or illness. While the levels of the autistic children were high, they were not as high as expected. (Note: My experience thus far has shown inconsistent/scattered levels, with some Autistic children being high, while others are low or normal. Interferon could possibly be a potential marker to distinguish different groups, but is routinely subject to multiple influences.) Other preliminary evidence suggests that a subgroup of autistic children have elevated levels of other cytokines (INF is considered a cytokine, a soluble substance that is secreted by cells that affects other cell functions). It is this author's opinion, that the "true" pathophysiology lies in these other cytokines, rather than alpha interferon. Research is urgently needed to sort these factors out and open new doors.
Now, since Dr. Goldberg has seen scattered results, it appears he started looking at other cytokines. So.... at this point, he seems to think that there are three distinct groups of NIDS. I hope I did not confuse all of you more but I do wonder if Dr. M mispoke and meant something else that was 100 percent positive with the XMRV retrovirus.