Author Ken Singleton, M.D.
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Key Players of
the Innate Immune System
The macrophage is a type of white blood cell whose function is similar to that of a member of a scouting party. The macrophage’s job is to roam or “scout” around the body looking for trouble, such as foreign invaders like Lyme spirochetes. Some macrophages are stationed in specific organs (such as Kuppfer cells in the liver). Others, called “monocytes” in your white blood cell blood test, roam around freely in the blood, from which they can go into body tissue when needed. If the macrophage encounters an invader while making its rounds, its duty is to sound the alarm, send out distress messages, and begin the battle while help is on the way.
The Natural Killer Cell
The natural killer cell, also known as the “NK” cell, is a critical member of the innate system team because it is able to independently seek out infected cells and, in many cases, cause instant destruction of foreign invaders. That is to say, the NK cells do not require recognition of a specific foreign antigen in order to attack and kill the enemy. The NK cells are said to be “cytotoxic,” meaning that they kill cells. In fact, they can instantly kill any cell containing a foreign invader or a tumor cell.
The NK cells fall into the category of white blood cells called “lymphocytes” on your white blood cell lab test. Lyme probably cannot be adequately controlled by the body unless the NK cells are performing their function adequately. Many Lyme-aware physicians believe that the blood level of a specific NK cell called the CD57 cell is an excellent predictor of when a person can come off of antibiotics. When the CD57 is high, then the NK cells (and the rest of the immune system) can handle Lyme without further need for antibiotics. When the CD57 is low, then the immune system is not strong enough to handle Lyme without the help of antibiotics. We will have much more to say about the NK cell later in this chapter.
NK cells are perhaps the most lethal weapon in our innate system’s arsenal against Lyme disease and related co-infections. NK cells are able to identify foreigners that are “not-self ” and instantly destroy them on contact in defense of “self.” The foreign invaders could be infectious in nature or malignant tumors. The NK cells in our bodies are absolutely critical to our survival upon exposure to any of these invaders. Because of this fact, we should be doing all that we can to support these immune system “warriors.” As I mentioned above, many Lyme-aware doctors believe that the NK cell is the major key to a successful outcome with Lyme treatment. Because of this fact, we often measure the levels of one of those NK cells called the CD57 on a regular basis when we are treating chronic Lyme disease.
There have been many studies that have shed light on NK cells. As a result, we know much about both the helpful and the unhelpful factors related to these cells. Factors that have been found to be unhelpful (and actually harmful) to NK cells include exposure to environmental chemicals, such as pesticides and herbicides. Even general anesthesia may temporarily lower NK function, which explains why many people catch colds soon after a surgical procedure. Chronic viruses frequently cause problems with NK cells (such as Epstein-Barr virus and HIV virus). Chronic fatigue syndrome and various autoimmune disorders have also been associated with NK cell abnormalities.
The normal aging process and chronic stress also appear to have an adverse effect on NK cells. Excessive strenuous exercise of greater than one hour may have a temporary negative effect on NK cells. Nutritional deficiencies have clearly been shown to cause poor NK numbers and function, especially deficiencies of vitamin C, B12, B6, beta carotene, and zinc.
Finally, anything that depletes the cells’ reserves of an important antioxidant called glutathione (GSH) may have an adverse effect on the killing power of the NK cell. The most notorious culprits for glutathione depletion are alcohol consumption and misuse of acetaminophen (the active ingredient in Tylenol). Acetaminophen should be used in low doses only and never on an empty stomach or with alcohol.
Another problem for the immune system is cigarette smoking. Smoking depletes the body of vitamin C. When cigarettes and alcohol are used together, the result is depletion in the body of both vitamin C and glutathione. This combination results in a severe compromise of two of the body’s most critical antioxidants. This will often severely impair the NK cell function, which greatly reduces the immune system’s ability to fight invaders.
Cytokines are chemicals that are secreted by various cells of the immune system. Both innate and adaptive cells can produce these substances. One of the first things that macrophages do is to secrete several types of cytokines to attract help from other members of the immune system. Therefore, cytokines act as messenger molecules (like telegrams) that help direct various components of the immune system. They also serve other functions, including helping white blood cells to grow and mature, all aimed at mounting the necessary attack to repel the enemy.
When it comes to Lyme disease, there are two vital opposite functions of cytokines: pro-inflammatory cytokines and antiinflammatory cytokines. By definition, the pro-inflammatory cytokines increase inflammation in the area of infection in order to help the immune cells get rid of the infectious organism. The anti-inflammatory cytokines reduce the inflammation in order to reduce collateral damage to self. From start to finish of an infection, the body is constantly secreting both of these types of cytokines in a very delicate balance in order to eradicate the invader with minimal harm to the body.
Going back to our tidal example, when the pro-inflammatory cytokines are dominant, the body is at daytime low tide (which is “seek and destroy” time). When the anti-inflammatory cytokines are dominant, the body is at nighttime high tide (which is “repair and replenish” time). Some of the major components of this cytokine group include:
|| Anti-inflammatory cytokines
| Interleukin one (IL-1)
||Interleukin ten (IL-10)
|| Interleukin four (IL-4)
|Interleukin twelve (IL-12)
| Gamma interferon
|Tumor necrosis factor
Adaptive System Key Players (Specific Immunity)
Shortly after the battle begins, under the direction of the macrophages (and their cytokines), certain other white blood cells in the lymphocyte family are stimulated to form specific T lymphocytes. The process is somewhat complex.
As I stated, the job of the innate system’s scout, the macrophage, is to gather information. Armed with that information, the macrophage wants to facilitate the active involvement of the more powerful adaptive system. The way the process occurs is that the macrophage first ingests and then digests some of the foreign invaders. It then is able to convey (or present) the specific information about that enemy to a T lymphocyte cell. The T lymphocyte that this information is presented to can then mature (or differentiate) in one of two directions, becoming either “helper” T cells (also called CD4 cells) or “suppressor” and “cytotoxic” T cells (also called CD8 cells).
In the discussion of Lyme disease, we are primarily interested in the helper T cells, also known as the CD4 cells. The helper T cells (CD4) can further divide into one of the following three kinds of CD4 cells:
-Th1 cells (which stands for “T helper one” cells), which secrete the pro-inflammatory cytokines mentioned above and are very effective at killing invading germs (even those inside of cells), but may cause potentially damaging excessive inflammation
-Th2 cells (which stands for “T helper two” cells), which secrete the anti-inflammatory cytokines mentioned above and also direct the cells that produce antibodies to begin their antibody production
-Treg cells (which stands for “T regulator” cells), which “regulate” the balance between Th1 pro-inflammation and Th2 anti-inflammation
All three CD4 components are critical to the successful control of Lyme disease. At the onset of Lyme infection, the Th1 response is vital to controlling Lyme. But the Th2 response is important to “cool off ” the Th1 and to produce antibodies for help to control Lyme. Finally, the Treg response is absolutely necessary to keep the system balanced. That is to say, the Th1 system tends to suppress the Th2 system and vice versa—a process similar to a see-saw. The Treg system keeps things in balance.
Here are some examples of how problems can occur when the T cell system does not work properly.
Example one: When Lyme invades the body, it wants to avoid the Th1 response, because that is the most deadly immune system attack on it. Therefore, Lyme actually induces the body to make IL-10 (an anti-inflammatory cytokine) for the purpose of suppressing the Th1 response. If the body’s Th1 system is not strong enough to overcome the premature Th2 (IL-10) suppressive action, then Lyme can penetrate deeper into the body tissues. Therefore, a Lyme-weakened Th1 (from excess IL-10) response will allow Lyme to successfully invade the body.
Example two: As previously stated, Lyme causes excess IL-10 production. But there are situations in which the body may already be in a state of overproduction of IL-10. This preexisting excess IL-10 condition is called “Th2 dominance.” Th2 dominance is a setup for a poor outcome from Lyme. Conditions such as chronic fatigue syndrome, chronic viral infections (like Epstein-Barr virus), mercury overload, parasitic infections, and chronic allergies all lead to the Th2 dominant state. In that state, the Th1 is suppressed not only by Lyme but also by the other situations that we just mentioned. Once again, the Th1 is limited in what it can do and Lyme is able to establish itself in the body.
Example three: In either of the above examples, if Lyme has successfully invaded, the Th1 system continues to try to attack The Lyme Disease Solution 1 4 4 Lyme but unsuccessfully. In this circumstance, there are four possible reasons. The first reason for this lack of success could be due to Th1 weakness/exhaustion (for example, if nutritional deficiencies are present). The second is that it could be due to ongoing suppression of Th1 by Th2. The third possibility is that a person has ongoing co-infections such as Babesia or Bartonella. Finally, it could be due to Treg’s lack of regulation of the process. I believe that the unfortunate result is that the weakened and inadequate Th1 system loses its ability to distinguish infected tissue from “self tissue.” This leads to what we call “autoimmunity” and chronic inflammation (which I will discuss in the next chapter). This is very frequently the picture of a typical Lyme patient when coming into a Lyme-aware doctor’s office—a long history of inadequately treated, active, or persistent Lyme with accompanying autoimmune manifestations.
Most of the time when we think about Lyme and the immune system, we have the tendency to think about antibodies. This is because the blood tests that are done to detect Lyme most often involve measuring levels of antibodies directed against Lyme. The antibodies measured by Lyme testing involve two classes of antibodies—(1) the IgM antibody, which is large in size (limiting its tissue accessibility), potent in enhancing the immune response, and produced in the first two to three weeks of Lyme infection and (2) the IgG antibody, Lyme Disease and Your Immune System 1 4 5 which is smaller (and more accessible to tissue), more specific to the infecting antigen, and comes later when the body is nearer recovery.
By definition, antibodies (also called immunoglobulins) are proteins produced by cells in the body called “B cells.” The goal of an antibody is to seek out and then attach itself to an invader like the Lyme spirochete. After antibody attachment, the other immune components then spot the tagged invader and come in to finish the job by destroying the germ. Most of the antibodies are produced in the adaptive immune system under the direction of the Th2 system and are very specific for a particular germ’s body parts (called “antigens”).
As an interesting sidebar, in addition to the Th2-directed antibody production in the adaptive system, there are also “natural IgM antibodies” produced by the innate system. The cells that produce these nonspecific antibodies are innate system cells called “B-1 cells.” It may be that these nonspecific antibodies are very important in the initial control of Lyme, even while the spirochete is still inside the tick. Some Lyme experts believe that high levels of these natural IgM antibodies may be the reason some people do not contract clinical Lyme when exposed to it by a tick bite. When the innate system is working well, with macrophages, NK cells, and the B-1 cells all able to do their job effectively, the body has an excellent chance of winning the war it faces, from infections to cancer. When both the innate and the adaptive systems are functioning efficiently, the body has an advantage over any potentially lethal foreign invader.
Additional Key Players
In addition to the immune system itself, healthy immune function is supported by other components in the body. Two particularly key players in this regard are the adrenal glands and chemical messengers known as endorphins.
The Adrenal Glands
The adrenal glands play a key role in the balance of the immune system because of their production of cortisol. Cortisol is a hormone that helps to “cool down” the immune system after it has accomplished its tasks in defending against harmful, invading microorganisms. This cool-down occurs in the following way.
One of the cytokines secreted by macrophages is known as IL-1B. Among its many functions, IL-1B sends messages to the brain’s hypothalamus, instructing it to release corticotrophin-releasing hormone (CRH). CRH then stimulates the pituitary gland to produce adrenocorticotropic hormone (ACTH). ACTH, in turn, instructs the adrenal glands to secrete cortisol to help regulate the inflammatory response that the macrophages are involved in. If we did not have this mechanism in place, we could die of overwhelming inflammation when we contracted an infection.
However, there are two potential problems with regard to cortisol production. The first problem is that, due to stress, the adrenal glands go into overdrive, overproducing cortisol. This condition is called “adrenal stress.” This scenario can result in excessive immune system suppression due to too much cortisol being produced. This resulting suppression can help Lyme bacteria to escape detection by the immune system, thereby helping the bacteria to survive.
The second problem occurs due to chronic stress, which can cause the adrenal glands to become overworked and exhausted. This condition is called “adrenal fatigue.” This scenario can result in inadequate cortisol production which, in turn, can lead to damage to healthy tissues due to uncontrolled inflammation. In this case, it may require taking physiologic doses of cortisol by mouth to help the adrenals until they can recover.
For both of these reasons, it is important that adrenal function be assessed in most patients with chronic Lyme disease. When adrenal function is impaired, adrenal support may be necessary. This support can be achieved using certain herbal remedies, as well as other natural supplements. The key items that are clinically useful include vitamin C, vitamin B5 (pantothenic acid), magnesium, eleutherococcus (Siberian ginseng), schisandra seed, rhodiola, green tea, grape seed and skin, licorice, and others. Again, when documented by laboratory testing, it may also be necessary to use temporary low dose oral natural The Lyme Disease Solution 1 4 8 cortisol (using adrenal replacement doses, not immunosuppressive doses) until the exhausted adrenal glands can recover enough to do their own job. Another key component of adrenal support is adequate uninterrupted sleep. (I recommend ideally seven to nine hours per night with at least five of those hours uninterrupted.) I will discuss adrenal and other endocrine gland issues in more detail in chapter 7 and the major problem of sleep deficiency in chapter 8.
As with the adrenal glands, endorphins also play an important role in maintaining healthy immune function and are critical to the control of Lyme disease. Endorphins are natural opiate-like substances produced by the body to help control pain. They are produced in the body during nighttime, with peak production occurring between 2 and 4 a.m. During waking hours, they are used by the body in various bodily systems including the nervous system, endocrine system, and immune system.
In addition to their pain-relief properties, endorphins also have very powerful immune system effects. For instance, the natural killer (NK) cells have endorphin receptors on their surfaces. When endorphins are present, the NK cells increase in number and in function by as much as 300 percent. Exercise is known to enhance NK function. The NK immune enhancement that derives from exercise is totally mediated by the effect exercise has on increasing endorphins. In fact, studies have shown that the administration of an endorphin receptor antagonist (which blocks the effects of endorphins on the NK cell) to a person exercising totally eliminates any immune system NK enhancement induced by exercise. In addition to exercise, endorphins may be increased also by massage and touch therapy, acupuncture, laughter, core body temperature elevation, and dark chocolate (without sugar please).
It is my belief that many patients with chronic Lyme disease are “endorphin-dysregulated” (that is, the production of endorphins has become chaotic and unregulated). For this reason, Lyme patients are, therefore, more susceptible to Lyme-related autoimmune disorders. Because this is so, restoring healthy endorphin production is essential when treating Lyme disease. In chapter 7, I will discuss a novel treatment for endorphin-dysregulation that has dramatically helped many of my Lyme patients.
If you would like
to learn more about the book before ordering it, feel free to browse
these excerpts, which are available online, free of charge:
of Contents • Introduction
and Diagnosis • Natural
Killer (NK) Cells
Diet • Medical
History and Physical Exam
Dose Naltrexone (LDN) • Food,
Diet, and Omega Fatty Acids
and Positive Outlook • Index
"What I have accomplished with this 500+ page book, The Lyme Disease Solution, is to share my everyday knowledge and practical experience of 10 years as a Lyme-enlightened practitioner (who also is himself a Lyme-survivor). Although I hesitate to use the “cure” word in relation to chronic Lyme, the principles in this book have resulted in a greater than 90% response rate in my patients. At least 60% of my patients achieve long-term improvement that allows them to get off of antibiotics completely."
— Ken Singleton, M.D.
THE LYME DISEASE SOLUTION
By Ken Singleton, M.D.
Foreword by James A. Duke, Ph.D.
Paperback Book, 523 Pages, $29.95 + $7 Shipping & Handling
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