What TNF-alpha and Neopterin Tell Us About the Immune System in Autism. Reasons for Hope: Lessons from HIV and Hepatitis.

Ok – forgive me but I had to laugh when I found this on graphic on the web.  It actually does a great job of explaining things. BUT!!!! (I know it is really complicated – but wait and all this will get explained).


Source: http://www.thetenthparadigm.org/mcs09.htm (an excellent discussion of ME/CFS by Professor Pall)

This graphic explains why I tell patients to avoid nitrous in the dentist office, why we observed increased oxidative stress and neopterin in autism, why Dr Chez finds high TNF-alpha in the CNS of children with autism, why anti-inflammatories like spironolactone and pioglitazone (Actos) help, why I tell parents too much calcium is a BAD thing,  why ATP (energy reserves are bad in ASD), why we think they have mitochondrial dysfunction, and why Enbrel helped a 53 Italian woman to regain part of her missing life.

For me after years of looking into this mess we call autism, this one picture affirmed more for me than I can easily relate.

Neopterin in ASD often runs 2-5 x higher than typical children – who are not ill.  Any acute infection kicks up the level of neopterin.

Neopterin comes from an activated immune cellular response.  We think that if neopterin remains elevated ALL the time that demonstrates viral persistence: as in HIV and Hepatitis. But it also means autoimmunity.  It also predicts the severity of atherosclerosis and a host of other disorders.

Neopterin in generated AFTER TNF-alpha is produced. TNF-alpha is produced AFTER NF Kappa B is transcribed from the DNA. It means the macrophages have been given the message (NF kappa B > TNF-alpha) to attack and macrophages are supposed to eat viruses and bacteria.


Graphic: Stylized macrophage attacking viruses like a PacMan game.

In hepatitis and HIV neopterin is elevation is typically seen in direct relationship to higher viral loads – whether we are talking about blood or spinal fluid.  This link is to a website dedicated to exploring the details of neopterin.  http://www.neopterin.net/hiv.htm


The immune system is trying really – really hard to get rid of viruses, but it isn’t working.  The high neopterin means high immune activation and it also seemingly paradoxically means high levels of virus.  You might think – hey what’s up? High immunity should get rid of the virus.  And you would be right IF that was all there was to the picture.

So what is keeping the immune system from functioning? In a nutshell the macrophages are blinded and cannot find their targets.  They are getting the message to fight, but then they cannot find the enemy.

Tomorrow I will explain what I think has happened in autism. The good news is I think we have enough pieces of the puzzle now to make sense of the immune catastrophe we label autism.

About Dr Bradstreet
Dr Bradstreet is a graduate of the University of South Florida College of Medicine and received his residency training at Wilford Hall USAF Medical Center. He is a Fellow of the American Academy of Family Physicians. He is an Adjunct Professor at the Southwest College of Naturopathic Medicine in Arizona. He is extensively published in the peer-reviewed literature on subjects of autism, oxidative stress, mitochondrial disorders, virology, hyperbaric oxygen, and toxicology (especially heavy metal chelation). He is trained in the the isolation and use of stem cells.

6 Responses to What TNF-alpha and Neopterin Tell Us About the Immune System in Autism. Reasons for Hope: Lessons from HIV and Hepatitis.

  1. marilina says:

    as always , sorry for my english…..
    1) energy balance of our childrens is precarious: what we found in these years of biomedical for example, is the mismanagement of the sugars, but also the difficulty to handle oxygen because of their inability to breathe properly (for example, my daughter can not dispense the breath …… she falled in hyperventilation, she can’t have deep breathing …., physical exertion in sport is managed with very great difficulty): in this generaL context , specifically, WHY ATP is not recommended?

    2)if macrophages are blind …… what happens? is there is an overproduction of something else than antibodies? the theory of mastocytosis in autism comes into this picture?

    • I think we are missing something in translation. But to be clear the effect of chronic immune activation is to steal – reduce energy production by decreasing the amount ATP manufactured.

  2. marilina says:

    the effect of chronic immune activation is to steal-reduce energy production by decreasing the amount of ATP manufactured.

    therefore, administer ATP , “helps” chronic immune activation?

  3. Ralph says:

    Dr. Bradstreet –

    Why exactly is too much calcium a BAD thing? How much calcium is the right amount? For those of us using “special diets,” is calcium supplementation acceptable?

    • Great question. Think about nature for a moment. Osteoporosis is extremely uncommon in the wild. How can a whale or elephant despite a huge skeleton pull if off and we struggle. In a nutshell most of what we thought we knew about calcium requirements is wrong and in truth had to be wrong since our diet could never provide that much calcium. So what’s up? not our Vitamin D levels for sure. Vitamin D def is common p very common. Levels are adequate in less than 10% of my patients. So a little calcium and the right amount of Vitamin D and we are fine. 100 to 300 mg of calcium balanced with an equal amount of magnesium and keeping Vit D levels above 60 should be fine.

      • Doron says:

        Does it make sense to match the high intake of Vitamin D with a higher intake of Vitamin K?
        It should solve both the “reduced bone cortical thickness” issue for boys on a GFCF diet and lower the free blood Calcium.

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