The Cytokine Storm as an Inflammatory Reflex

Relatively recent research has revealed a truly extraordinary connection between the brain and the body; between the vagus nerve, the immune system, and the autonomic system. All of which depend upon energy produced by the mitochondria and thus are dependent on thiamine. Before I embark on a description of this research, a few definitions are required.

• Vagus nerve: This is the longest nerve in the body. There is one on each side and the right side nerve has a different action from the left side nerve. Both start in the brain and both go to the spleen, the lung, and the intestine. It is able to send signals to and from the brain to the body. The name comes from the Latin word meaning “wanderer”.
• Cytokine: There are many of these in the body. They are small proteins, some of which cause inflammation and some inhibit it.
• Cytokine storm: If and when the inflammatory cytokines get out of control their profusion is called a cytokine storm.
• Inflammation: A localized physical condition induced by cytokines in which the affected part of the body becomes reddened, swollen, hot, and often painful, especially as a reaction to injury or infection. We now know that the inflamed joints in rheumatoid arthritis are caused by inflammatory cytokines and might justify that disease as a form of dysautonomia.
• The spleen: An organ that is located in the upper left part of the abdomen. It produces lymphocytes which are important elements in the immune system. It is the largest lymphatic organ in the body.
• Macrophage: This is a type of white blood cell of the immune system that engulf and digest cellular debris, foreign substances, microbes, and cancer cells, in a process called phagocytosis.
• The autonomic nervous system (ANS): It has been emphasized in many posts that we have two different nervous systems. The voluntary system responds to free will whereas the ANS acts automatically. It is controlled by the lower part of the brain and this will be important as we develop this post.
• Acetylcholine: A chemical substance known as a neurotransmitter. Without this substance, the vagus nerve will not function.
• Citric acid cycle: This is a complex series of chemical substances that occur in nearly every cell in the body. It is the “engine” of the cell, manufacturing the energy required for the cell to function. This energy is stored in another chemical substance known as adenosine triphosphate (ATP). Although the analogy is imperfect, the nearest thing to explain its function is “a battery”. So you might think of the relationship as being like a continual recharge of a battery. Consumption of energy for function must be met by a continual production. It is the deficit between energy production and its consumption that causes the symptom that we call fatigue.

The Inflammatory Reflex, an Autonomic Response

The reason that I have called this a reflex is because we now know that inflammation, a defensive mechanism, is controlled by the brain through the vagus nerve. It is an automatic and reflexive response controlled by the autonomic system. The inflammation of selected parts of the body results from the release of inflammatory cytokines by the action of this nerve. That is why I think of rheumatoid arthritis as a form of dysautonomia (abnormal ANS function).

All of us live in an essentially hostile environment. We have to cope with an attack by microorganisms such as bacteria and viruses, different types of trauma, the weather, and virtually any outside or inside change that demands a response. In other words, we live our lives from one end to another in a state of attack and defense. I have indicated many times that any kind of response to some form of attack requires energy to run the machinery that acts in our defense. When energy is insufficient, the ANS begins to fail and defense mechanisms collapse or become distorted in their action. If severe enough, death may follow. Another cause of disease is faulty genetics but that is also partially energy dependent because of the science of epigenetics.

The ANS works all the time and is monitoring our well-being. It is able to detect an attack by a microorganism or other forms of “stress”. This results in a message, sent via the vagus nerve to the brain. It is essentially a notification that some form of attack has been detected. What happens then is so well described in an abstract from a published paper that I quote from it liberally below.

The ‘cytokine theory of disease’ states that an overproduction of cytokines can cause the clinical manifestations of disease. Much effort has been expended to determine how cytokines are regulated in normal health. Transcriptional, translational and other molecular control mechanisms protect the host from excessive cytokine production. A recent discovery revealed an unexpected pathway that inhibits macrophage cytokine production. The inflammatory reflex is a physiological pathway in which the autonomic nervous system detects the presence of inflammatory stimuli and modulates cytokine production. Afferent signals to the brain are transmitted via the vagus nerve, which activates a reflex response that culminates in efferent vagus nerve signaling. Termed the ‘cholinergic anti‐inflammatory pathway, efferent activity in the vagus nerve releases acetylcholine (ACh) in the vicinity of macrophages within the reticuloendothelial system.

Some of the cytokines cause inflammation while others inhibit inflammation. A growing body of clinical data suggests that a cytokine storm is associated with Covid-19, suggesting that it might be an important component for rescuing patients with severe Covid 19.

The Energy Immune Response Hypothesis

I have done my best to describe the vitally important relationship between the body and the brain in defending ourselves from the attacks of environment. By far the most important phenomenon seems to be how we produce energy and I learned many years ago that beriberi was the prototype for failure of energy production. Thiamine was blamed as the cause of this disease and in spite of the importance of other members of the B complex, it seems to be the dominant vitamin in the consumption of glucose to provide energy to the brain. We have good reason to believe that an insufficiency of this vitamin is all too common in the United States and is responsible for a huge amount of unrecognized disease. Because the lower part of the brain that controls the ANS is particularly sensitive to this deficiency the commonest result is different manifestations of dysautonomia. However, patients are not visibly affected, as seen by others, often visiting their family physician where a common false diagnosis is psychosomatic disease. The general effect is a lack of fitness that makes them more susceptible to the more severe results of any infection.

The Cytokine Storm, the Vagus Nerve, Acetylcholine and Thiamine

If cytokine pathology is responsible for the symptoms of Covid 19, stimulation of the inflammatory reflex is an obvious method of treatment. This can be done by electrical stimulation of the vagus nerve. However, if thiamine deficiency is a common finding in the American public, it would result in a deficiency of acetylcholine, the neurotransmitter essential to the vagus nerve. It strongly suggests that thiamine, used as a drug, might be successful in suppressing the cytokine storm. The most effective thiamine derivative would be thiamine tetrahydrofurfuryl disulfide (TTFD). Because my years of study have demonstrated to me that there is no toxicity arising from it, it could be used empirically in the emergency room, although if given to someone with long-standing chronic thiamine deficiency, there is a possibility of refeeding syndrome. If this is the correct solution to the symptoms of Covid 19, it may well be that thiamine deficiency is responsible for those that are generated in the so-called Longhaulers. The chronicity of symptoms is the same as those that occur in beriberi.

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