There are many different factors involved in leading the immune system a stray. Most of the time, several are occurring simultaneously. This is crazy making when trying to sort out whether symptoms are caused by dietary, physical, hormonal or mental influences. Many healthcare providers will pick their favorite and treat only that. Very few would consider how microbes can manipulate our systems for their survival. Yet directly contribute to the perpetuation of autoimmune conditions.
For more than 30 years T-helper (TH) cells have been divided by immunologists into two functional subsets: Thelper-1 (TH1) and T-helper-2 (TH2). TH1 and TH2 subsets are characterized by a distinct activity of and pattern of cytokine-secretion. Decades of research went into understanding the role that TH1 autoimmune T-cells play in neuro-endo-immune (NEI) inflammation. Although some Alternative practitioners in implementing therapeutic interventions use the assessment of TH1 and TH2 cytokines as a guide for intervention, it is the TH-17, which has emerged as the most pathogenic helper cell meriting possible Functional Medicine intervention.
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Despite its seductive simplicity, the TH1/TH2 model does not adequately explain T-cell immunity. Many cytokines produced by T-cells do not fit obviously into either category. Recent studies have shown exposure to lectins or bacteria trigger T-cells to produce IL-6, IL-17, and GM-CSF, cytokines not associated with either the TH1 or the TH2 immune system.
The Role of TH17
The latest T-helper to be defined, TH17, together with its cytokine family of IL-17, has been deemed the most pathogenic in inflammatory NEI conditions and autoimmune disorders. Although IL-17 is highly pathogenic, as evidenced by its presence in a variety of inflammatory disorders, its initial intent is not destructive. TH17 plays a protective role in host defense against infection, by inducing chemokine and GCSF expression from surrounding cells thereby recruiting neutrophils and macrophages to infected tissues.
Within the intestinal mucosa, naturally occurring TH17 cells control a variety of bacterial and fungal infections at the mucosal surfaces. It is in the presence of chronic inflammation that TH17 becomes destructive and over produces IL-17.
IL-17 stimulation of TH17 contributes to the onset of multiple autoimmune diseases including allergic inflammation, rheumatoid arthritis, autoimmune gastritis, inflammatory bowel disease, psoriasis and multiple sclerosis. This activation of the inflammatory response system is induced by different pathogenic factors, such as gut bacterial endotoxins resulting in progressive neurodegeneration by TH17 cells. Through the understanding of the role of bacterial endotoxins and other pathogenic factors in the induction of autoimmune diseases by TH17 cells.
Bacteria Stimulation of TH17 Immune Response
Lipopolysaccharides (LPS) are the major cell wall components in bacteria. Almost 90-95% of gram-negative bacteria are considered to be harmful for the host. In other words, they are pathogens. Obviously, if the immune system successfully recognizes, consumes and destroys all the bacteria that are present in any given infection, the bacteria has failed to establish itself in the body and cannot cause disease.
However, the immune system does not always succeed in its task. Often the reason for this failure is that the invading bacteria or other micro-organisms have evolved a strategy for evading or suppressing the host’s immune response to that organism.
Bacteria are extremely versatile microorganisms that continuously sense the gastrointestinal environmental conditions and can rapidly alter their behavior and appearance to survive and reproduce. This process enables the bacteria to hide without provoking an inflammatory response from the immune system.
The measurement of multiple cytokines will present the CAM practitioner with a broader picture of the patient’s inflammatory condition, and thereby would be useful in fitting a therapeutic intervention on an individual basis. – Vojani
A common method of evasion is suppression of pro-inflammatory cytokines. The microbes target those cells of the immune system that specifically react against them. By disabling or suppressing those cells, the microbes prevent the body from mounting an immune response. The Endotoxin lipopolysaccharide (LPS) causes a reduced ability to produce pro-inflammatory cytokines. Exposure to LPS influences cytokine production resulting in a shift toward a TH2 cytokine response when bacteria should cause a TH1 response. This would cause mixed results for those doing a TH1/TH2 Challenge. Many of the NEI Stimulated Cytokine test results showed a mixed TH2 and TH17 immune response.
Small intestinal bacterial overgrowth (SIBO)
Small Intestinal Bacterial Overgrowth (SIBO), also termed bacterial overgrowth, is a disorder of excessive bacterial growth in the small intestine. When bacteria migrate into the upper sections of the small intestine, they are no longer beneficial becoming detrimental to health. SIBO bacteria produce more toxic substances some of which alter hormone elimination.
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SIBO causes a several issues, – altered hormone levels, altered neurotransmitters and cytokines, altered gut environment, and altered microbial behavior to name a few.
When SIBO occurs, Clostridia species of bacteria convert bile salts into toxic bile salts. Toxic secondary bile acid levels are damaging to the cells lining the small intestine and cause extensive mucosal damage of the stomach and esophagus. This is more harmful than acid reﬂux alone. The major conversion of secondary bile salts is the formation of lithocholic acid. Lithocholic acid competitively inhibits etiocholanolone elimination occurring in the liver. This results in increase potential for immune stimulation and a localized fever. In addition to this lithocholic acid causes damage to Vitamin D receptors and reactions to sunlight or Vitamin D supplments.
Etiocholanolone is a little known hormone that is produced just after DHEA. Actually etiocholanolone is produced from androstenedione. Etiocholanolone is responsible for producing short-term inflammation with symptoms of chills, anorexia, headache, malaise, muscle pain, joint pain, and inflammatory responses.
Excessive DHEA supplementation may be the cause of high etiocholanolone levels. Certain individuals have episodic bouts of inflammation or fever due to periodic accumulation in the blood of unprocessed Etiocholanolone. Some may describe these episodic bouts as hot flashes.
If a lab test report DHEA, androstenedione and testosterone levels are low with signs and symptoms of bacterial overgrowth. Etiocholanolone may be causing the symptoms of inflammation, fever, increased WBC, increased serum C-reactive protein, low iron (hypoferremia), increased White Blood Cell activation and activity.
Hormone Replacement Therapy
Occurring naturally or through Hormone Replacement Therapy, increased estrogen tends to have a stimulatory effect on the immune system, while testosterone tends to have suppressive effects. For example, estrogen enhances the secretion of the cytokines IFN-γ, IL-1, and IL-10. Testosterone generally decreases the secretion of the cytokines IFN-γ, IL-4, and IL-5.
Microbial Survival Strategies
Neuroendoimmunology is an emerging field of medical science that seeks to understand the interconnectedness of the nervous, endocrine, and immune systems functioning as a larger whole, termed the “NEI Supersystem.” These three systems communicate to maintain balance in your body using neurotransmitters and cytokines of which there are essentially two different types – those that relay the message to stop or slow down.
Think of these as the off switch or the brakes on a car. The others relay the message to start or speed up. These would be the on switch or the gas pedal on a car. In your body just as when you are driving your car there are times when you need to start or stop the car, go faster or slower, stay with traffic or slow down out of traffic. Inhibitory neurotransmitters and anti-inflammatory cytokines slow or stop responses. Stimulatory neurotransmitters and inflammatory cytokines start or speed up responses in the NEI supersystem.
Read More: How Neurotransmitters Affect Your Life
Microbes know this and hack into the NEI Supersystem manipulating the responses for their own survival. Over 95% of neurotransmitters are made in the gut. This gives the microbes easy access to the cells that make them. In a healthy gut with good barrier variables (gut lining) there is a tolerance for microbes as long as they honor their barriers and do the job required of them.
The most important thing to understand about microbes is the environment controls their behavior. An example would be a metropolitan city. The environment in the ghetto controls the behavior of those who live there, just as the good neighborhood controls the behavior of those inhabitants. The majority of people living in both neighborhoods are good people. It is the environment that changed their behavior.
In the gut, the majority of microbes are good. However in a Ghetto Gut, the good microbes alter their behavior. Subtle changes in gut chemistry, enzymes or pH have a profound affect on them changing their behavior from beneficial to toxic. They need a place to live on the gut lining. A damaged lining leaves limited living space. The microbes start forming protective multicultural colonies by building biofilm like a “crack house” moving into your neighborhood. You may know these as polyps in the gut, plaque or tartar in the mouth. No digestive chemistry, white blood cells or antibiotics can penetrate the biofilm.
Microbes will increase the production on anti-inflammatory cytokines to calm the immune system. While at the same time the dendritic cells monitoring the contents of the gut are sounding the alarms by sending out the stimulatory neurotransmitters and inflammatory cytokines for the immune system to deal with the invaders.
This over-production of stimulatory neurotransmitters then spills over into other systems causing increased excitation. The feedback control then starts releasing inhibitory neurotransmitters to shut down those systems. Think of someone pouring water into a glass. They are watching the water rise and stop pouring when the glass is full. This is the way the system should work. A signal goes out for a hormone to be produced and when the proper amount is made the production stops.
However when microbes hack into the system, these external (although they are in your gut) forces alter the feedback messages creating a constant demand for inhibitory neurotransmitters and inflammatory cytokines. Now, not only is the person pouring the water not paying attention but these hackers are also pouring. It doesn’t take long for the glass to spill over.
This depletes your body’s ability to produce and maintain balance of the neurotransmitters while at the same time the cytokines continue to direct the immune system to attack. This results in first episodes of Cytokine Storms and as the system collapses into Cytokine-Induced Sickness Behavior.
Microbes Act Like Skunks
For the microbes, it is turf warfare and they must constantly protect their territory. Some microbes literally act like skunks. These bacteria and parasites will release a spray of Nitric oxide when they sense the presence of danger from other microbes or the immune system. This super-antioxidant nitric oxide is used by White Blood Cells to kill microbes. By doing this, the white blood cells think the invaders have been taken care of and leave the bacteria or parasite alone. The problem is that there are several types of nitric oxide. The version produced by the microbes is the iNOS or inflammatory version.
Some microbes have the ability to make themselves invisible to the immune system. Helicobacter pylori are one example. First, H. pylori burrow into your stomach lining and eliminate their waste there, poisoning the cells lining the stomach. We now know this to be the main cause of stomach ulcers. This stops the production of stomach acid, which would kill the H. pylori raising the pH to a more alkaline level.
Why do Doctors still think it is because a person is producing too much stomach acid?
Once at their preferred alkaline pH, the H. pylori change their behavior and begin producing Lewis antibodies. Lewis antibodies make H. pylori invisible to the immune system and promote the onset of autoimmune gastritis. Autoimmune gastritis is frequently associated with autoimmune thyroiditis (Hashimoto’s) and other organ-specific autoimmune diseases. Despite this the Medical doctors continue to do “antibody” testing for H. pylori, which shows negative in a chronic infestation.
As we learn more there are likely other microbes that will be found that use stealth or mimicry as part of their survival strategy.
Parasites are Mobile
Parasites are mobile, moving much faster than the slow moving immune cells. Worms, especially punch holes in lining and moving away before the slow moving WBC can reach the site. Parasites and many bacteria and mold also damage immunoglobulins that are responsible for food sensitivities. This makes the immunoglobulins cross-reactive to any food commonly eaten. The result of this is a direct immune stimulation through the histamine or complement cascade.
Zombie White Blood Cells
Mycoplasma are strictly parasitic. When they start misbehaving, they will cause immortalization of our immune cells. When you do a blood test, if the Mycoplasma are involved, you’ll typically see white blood cells below four, and the absolutes – neutrophils and lymphocytes, down in the 1.8 to 1.5 range. Neutrophils, should have a life span, of 7 to 8 days, and lymphocytes 30 days to one year. The White blood cells dying sends a signal to make more. Studies are showing that Mycoplasma can actually cause neutrophils to live two years or more. Essentially becoming zombie white blood cells. Since they don’t die, the signal to make more never gets sent. What that does is that causes a chronic immune attack on the body. Cytokine control is lost because they never get any updates as to what they should and should not be sensitized to.
The fever producing effect of Etiocholanolone is due to the release of interleukin-1 (IL-1) from the white blood cells that are mobilized in response to the misbehaving gut bacteria. Failure of the liver clearance causes increased levels of etiocholanolone to arouse pro-inflammatory cytokines. Once stimulated by IL-1, Etiocholanolone will fire up IL-6, which is a TH17 pro-inflammatory cytokine.
The immune system is balanced with cells that respond to microbes by developing into cells that regulate the activity of the immune cells.
The activity of Th17 must be balance with development of regulatory T cells termed T(regs). When the activity of the immune stimulation is excessive and not balanced by regulatory cells of the immune system then there is the increased risk for development of autoimmune diseases. Therefore in many autoimmune diseases the activity of TH17 exceeds that of T(regs). Therapeutic supplement protocols for treatment of autoimmune diseases such as Hashimoto’s thyroiditis, Rheumatoid arthritis, or Multiple Sclerosis (MS) must focus upon immunosuppression, immunomodulation, or even immunoregulation of immune cells such as Th17.
Lectins strikingly increase levels of multiple pro-inflammatory cytokines (especially interleukin 2 receptor (IL-2), tumor necrosis factor alpha (TNF-α), IL-6, IL-8). Cytokines can produce an inflammatory response to food independent of the allergic reaction that most are familiar with. In this response the immunoglobulins (IgA, IgG, IgM & IgE) do not play any role. Food allergy testing will not detect a cytokine induced inflammatory response to food. Many cytokines are undetectable in blood because they are produced locally and have a very short half-life. This requires specialized testing done with the NEI Stimulated Cytokine panel that measures these cytokine and chemokines.
This requires reducing your exposure to the dietary lectin contained in ALL fruits and vegetables.
A Cytokine storm is more of a symptomatic condition, which occurs in varying forms, and involves a number of different mechanisms. The primary symptoms of a cytokine storm are extreme fatigue, low mood, anxiousness, anxiety, insomnia, high fever (intermittent hot flashes), swelling and redness, and nausea. (You may be more familiar with a cytokine storm known as Septic Shock, which is another example of the immune system gone berserk.) “Storm” may be an appropriate metaphor, acknowledging a variety of mechanisms in a variety of circumstances.
After the storm: Cytokine-Induce Sickness Behavior
After the cytokine storm has subsided, sick individuals have common symptoms of sickness, little motivation to eat, withdrawal from normal social activities, fever, burning muscles, aching joints and fatigue and have significant changes in sleep patterns. They display an inability to experience pleasure, have exaggerated responses to pain and brain fog. Proinflammatory cytokines acting in the brain cause sickness behaviors. Although Functional Medicine has defined proinflammatory cytokines as the central mediators of sickness behavior, for your unique circumstances a much better understanding of how the cytokines and neurotransmitters are communicating with each other is best done through lab testing.
The NEI Supersystem is self-regulating. For most people it is. However, with any finely tuned system, it does not take much to disrupt the entire process. It is imperative to restoring health, that the identity and behavior of the microbial hackers be determined to allow the restoration of the NEI Supersystem.
Much like a thermostat keeps the temperature in your house at a comfortable level. Now imagine your thermostat broke, what would happen? Which is system is supposed to run – heat or cooling? That is exactly like a Cytokine Storm, something knocks the balance out of your response system. One thing that is clear enough is that there must be negative feedback loops in the immune system, as well as positive ones. The latter enable the system to react quickly to serious infections. The former are needed to keep the system itself from spiraling out of control.
The measurement of multiple cytokines using the Neuroscience NEI Gold (Stimulated Cytokine and Neuroendo Comprehensive) lab test used at Wellness Alternatives will present Dr. Peterson with a broader picture of your inflammatory condition, and thereby would be useful in fitting a therapeutic intervention on an individual basis.
What is Stimulated Cytokine testing?
Stimulated Cytokine testing is intended to assess whether an individual’s symptoms could be attributed to an imbalanced immune response. Our goal is to understand as best we can where to target therapeutic interventions, minimizing emotional decisions and guesswork in the therapeutic protocol.
It’s important to note that the standard immune testing by itself cannot distinguish between an immune response that is currently in progress, and one that happened in the past. That’s because it cannot tell the difference between so-called “effector” T cells that are currently fighting an active infection, and “memory” T cells that responded years ago to a prior infection and continue to circulate in the bloodstream.
However, at the same time it’s important to recognize that even a test that measures up to 17 cytokines, as NeuroScience Stimulated Cytokines Comprehensive panel does, is far from actually being “comprehensive”, considering that over 100 cytokines have been described to date!
For more information go to Wellness Alternatives or call 530-615-4083 today!
Call today! 530-615-4083