Tinkering with the Immune System: Harmony is the Goal, But Can We Find It?
March 30, 2011 29 Comments
As we continue our discussions of the immune system dysfunction we are blaming for so much misery (Autism, Alzheimer’s, Inflammatory Bowel Disease, Diabetes, etc), I feel it is very important for you to understand we are messing with Mother Nature. We accept she is messing with us and we want to mess back, but finding that balance is more challenging than keeping blood sugar balanced for an insulin dependent teenager (and believe me – that is challenging).
DON”T MESS WITH MOTHER NATURE?
This is the work of Jonathan Wong – Very talented Artist
She looks a little scary in this depiction and that is the impression I wanted. Now let’s take a closer look at what we want to mess with.
http://www.ncbi.nlm.nih.gov/pubmed/19707398 links to the full open access paper I will discuss.
Now take a closer look at the left side of the diagram. See the macrophage? There is an arrow to an activated macrophage which in turn makes TNF alpha. So that is easy enough. Oh. but wait we have a problem. In cancer you would seem to want lots of TNF alpha to kill cancer cells but it doesn’t work. In fact, high TNF alpha means high neopterin (an important biomarker) and the higher the neopterin the worse the prognosis. That is also true for HIV infection: higher neopterin means higher TNF alpha and a worse prognosis. So what’s up?
“Neopterin is produced by human macrophages/monocytes when stimulated with interferon-gamma. Production of neopterin is found in serum, cerebrospinal fluid (CSF) and urine of patients with infections by viruses, intracellular bacteria and parasites, autoimmune diseases, malignant tumors and patients in allograft rejection episodes.” full paper online open access. [Gut Pathog. 2010 Aug 22;2(1):9.] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939532/?tool=pubmed
Now I have get you back to nagalase: alpha-N-acetylgalactosaminidase. This enzyme prevents the Vitamin D3 receptor from being activated on the surface of macrophages and with that they cannot properly activate. I don’t think we fully understand the function of the GcMAF receptor. Nagalase levels are high at the same time that neopterin is elevated. It would seem that shouldn’t be true if GcMAF was initiator of macrophage activation. It must be a bit more downstream from neopterin. To me, the likely scenario is that TNF sends the signal and part of the activation takes place – hence high neopterin and lots of macrophages, but as a result of nagalase activity the Vitamin D3 receptor looses its active site. But something about adding Gc MAF back into the system allows macrophages to kill cancer cells and rid the body of HIV: as noted in my discussion 2 days ago.
So my suggestion is some combination of GcMAF and perhaps Etanercept (Enbrel) may be able to bring us some rather tricky balance to Mother Nature’s combat zone. But a Warning here – as far as I know no one has ever done this.