Thank you Kronk for your encouraging words. Thank you Scott for referring me to Czabo.
The world of the herpes virus and the endothelium
Probably tucked deep inside our endothelium lies somewhere the viral cause of MS. The virus of the herpes family settles deep in the endothelium.
The virus itself is no longer detectable in the blood. An eminent immunologist once told me that the virus infection itself is removed from the blood within a day. Thus, there is more to it. We probably have to look for this low-level chronic EBV infection tucked deep inside the endothelium.
The immune system and the virus have evolved alongside, for millions of years, most probably for hundreds of millions of years. Even fish carry the virus. This article (unfortunately in Dutch) shines some light on the virus.
http://www.ntvn.org/artikel/pdf/2011-1_ ... enomen.pdf
What applies to CMV probably applies to all herpes viruses including EBV. Quote from the article:
The virus nests in the vessel wall, and occasional breaks out and causes major changes in the immune system by the formation of highly aggressive effector T-cells (CD4 + and CD8 +). This type of immune cells for their survival depends on the presence of the herpes virus and comes in healthy people only when they are infected with the virus which itself is no longer detectable.
The relationship between the well detectable CD4 + and the CD8 + T cells, and the virus means that the virus itself is somewhere in the body.
The fact that cytomegalovirus-like viruses are found in very many species – including in fish - suggests that it evolved along side with us for a very long time and adjusted itself entirely on the man. In fact, humans and virus keep each other in balance and the virus helped along the long, joint road through attack and defense to build up our present immune system. Unquote
The fat metabolism and the virus
Omega-3 is anti-inflammatory, probably because it suppresses the virus. Texas researchers suggested the effects of interferon may be attributed to virus suppression.
Omega-6 is not anti-inflammatory, it is said to be pro-inflammatory but whether and how the virus is involved is not clear to me.
The Omega-6/Omega-3 ratio in our diet has dramatically changed over the last 150 years, from 1:1 to 16:1. The emergence of inflammatory diseases corresponds/correlates. The articles set out the evolutionary aspects of our diet.
http://www.hindawi.com/journals/jnme/2012/539426/
http://www.sciencedirect.com/science/ar ... 2206002435
The last article explains how many chronic conditions, including cancer, cardiovascular disease, autoimmune diseases, rheumatoid arthritis, are associated with factors that increase by increases in Omega-6 fatty acid intake and decrease by Omega-3 fatty acid intake. The balance is important for homeostasis and normal development.
On the conversion of Omega-6 (LA to arachidonic acid AA an inflammatory precursor) and Omega-3 (ALA to anti-inflammatory precursors EPA and DHA), it is interesting to note that conversions occur along the same rate-limited enzymatic pathways, this means they “compete" for a spot.
Both Omega-3 and Omega-6 influence gene expression. Since many chronic diseases begin in utero or early in infancy, proper dietary intake of PUFA even prior to pregnancy may be important. It would thus seem that an ever weakening society could go across the boundaries of generations. Oh my God, I think this may be very serious and important.
Dietary Omega-6 fatty acids promote whereas marine Omega-3 fatty acids EPA and DHA inhibit leukotriene-mediated inflammation that leads to atherosclerosis.
Leukotrien is a potent fast acting lipid mediator. What is very interesting here is to find a clear relationship with the EBV:
http://www.eurekaselect.com/85606/artic ... nity-vitro
And this one: quote Preincubation of PMN with EBV resulted in an increased release of arachidonic acid .... These data indicate that binding of EBV to human PMN results in the activation of intracellular events involved in the release of pro-inflammatory lipid mediators.
http://www.ncbi.nlm.nih.gov/pubmed/11737068
Or this one: Importantly, the results indicate that endogenous LTB4 can induce T-cell activation that inhibits the EBV-induced proliferation of B lymphocytes.
Wow, this link of the fat metabolism with EBV is incredible. Have we arrived here at the very centre of MS? To the core of the inflammatory fat metabolism with a clear link to EBV?
Peroxynitrite: a natural immune reponse to the virus?
The microcosm at the submicron level of viral activity is poorly understood. Szabo suggested in this paper that peroxydation inhibits viral replication.
http://www.enzim.hu/~lbarna/articles/17667957.pdf
Is this peroxynitrite part of the immune defense mechanism? Or is the peroxynitrite just a consequence of the superoxide (the immune system) trying to kill the virus? That then reacts with the NO where besides the superoxygen also the peroxynitrite works against the virus?
Could it be that in the initial phase of MS there may be some limited suffering of normal cells due to the peroxynitrite while in our case the mechanism has tumbled over too far to the other side?
In conclusion, I think that the cause of MS is somewhere at the intersection of the lipid mechanism, the virus and immune action. There may be a number of other (side-)factors too that play a role such as psychological mechanisms in immune modulator (cortisol and cholesterol mechanism involved?), platelet aggregation (causing further nutritional failure?), the incorporation of EFA in cell membrane phospholipids etc.
http://pni.osumc.edu/KG%20Publications% ... 29/062.pdf
Letermovir would seem a potentially very promising drug that breaks the viral cycle, possibly at the submicron level.