Cory Tichauer, ND Immune Dysfunction and Chronic and Post-Treatment Lyme disease LDN 2017 Conference Presentation

Hi everybody. My name is Dr. Corey Tichauer, I'm a naturopathic physician with the Bear Creek Naturopathic Clinic here in Medford, Oregon. I've been in practice for 15 years focusing on the treatment of chronic infectious illness, environmental medicine, and immune dysfunction in chronic illness, neurodegenerative conditions, and a variety of functional problems the conventional medicine system struggles to treat. 

My talk today is on immune dysfunction and chronic and post-treatment Lyme disease, and how we can use low dose naltrexone to reduce the chronic inflammation associated with these conditions. The first thing I'd like to do is start with some definitions of terms.

Post-treatment. Lyme syndrome is a word that many people have heard of and probably struggled to understand because it's used interchangeably with chronic Lyme disease, and in fact, these are likely two different conditions, but yet both of them are present. Post-treatment Lyme syndrome is something that many clinicians who deal with this probably encounter these scenarios.

Patient feedback can be summarized by a few things. This idea that I've treated my Lyme infection aggressively yet I still continue to have symptoms, or every lab that I do is negative since I finished treatment, but I'm still symptomatic. You also hear if I stopped treatment my symptoms always come back. Some have to stay on therapy and otherwise all end up getting sick again. Or no matter how much treatment I do, no matter how many doctors I see, no matter how much I spend, I never feel completely better. I'm always sick. how many people actually end up having this phenomenon happen.

It's a rather common condition, unfortunately, and I think the numbers are pretty consistent with what I see in my practice, but it's been shown that 10 to 20% of patients will continue to experience lingering symptoms of musculoskeletal pain, insomnia, brain fog, and other functional conditions.

After single or even multiple treatment courses, 10 to 20% now that's a lot. Post treatment Lyme syndrome is defined as the persistence of symptoms more than six months following an effective treatment, and this is an effective treatment regardless of whether you're going to follow the infectious disease society of America guidelines.

It's three weeks of an antibiotic, or whether you're going to utilize international Lyme and associated diseases, society guidelines, and use more long term therapies on these people, but they're still symptomatic following six months of treatment, and that is post-treatment Lyme syndrome. 

Now let's juxtapose that with chronic Lyme disease. It is different from post-treatment Lyme disease syndrome, but it has similar symptoms. The difference between chronic Lyme and post-treatment Lyme is the organism itself, and I would postulate that in chronic Lyme disease, we're actually dealing with an active infection that is still causing tissue damage.

It's not the immune system that's solely responsible for the problem, but that this organism is still active. And chronic Lyme is a phenomenon that you see occurring for a variety of reasons, as I've described here. Some of them, inadequate treatment duration. Maybe they did need six weeks or 12 weeks or longer of treatment instead of three improperly chosen medications or therapies.

You know, the one day of doxycycline isn't going to work. Maybe you need more than one antibiotic. Maybe you need to add more herbs. Maybe you need to do other things or do hyperbaric or do Ivy or whatever. Presence of still undiagnosed or untreated co-infections, miss the Bartonella, Babesia, mycoplasma, whatever it may be, or comorbid conditions or other environmental illness.

For those of us working in this area, things like mold exposures, heavy metals are known to hamper the immune response and contribute to the persistence of active infection. And if you don't get out of those environments, you may not be able to eliminate this active organism.

The common denominator in both post-treatment Lyme syndrome and chronic Lyme disease is, I would argue,  bacterial persistence. There's a lot of argument between Eilat and IDSA about whether or not the organism is there and so on and so forth. And what I'm going to say is neither person is right and neither side is wrong.

The reality is that Borrelia likely survived in our bodies once we've acquired it. There are hundreds of studies that demonstrate that Borrelia can still be found in human hosts following multiple antibiotic rounds, and there's a lot to describe why this organism can continue to survive in a human host despite the use of these antimicrobial therapies.

And some of these, and this is certainly by no means exhaustive, include persister cells. It's been a hot topic in the last few years. It's described by doctor Zang and popularized a lot by Dr. Richard Horowitz, the presence of cystic forms of this organism, also known as round bodies. The ability for Borrelia to move into immune privilege sites where there's very poor capillary perfusion and the immune system is not able to access as well.

The ability of immune modulators in the host can actually reduce our ability to attack this organism. Biofilm formation, which shelters colonies of Borrelia and prevents antimicrobials from actually penetrating variation in surface proteins on the bacteria itself and plasma exchange, which prevents immune recognition, are all some of the contributing factors that we see that assist in the ability of this organisms to persist.

This is just a very short list of, I believe more than 400 citations I have on my computer alone showing that Borrelia can continue to survive in the human body.

As we sort of discussed this idea of chronic Lyme and post-treatment Lyme syndrome relating to bacterial persistence. We  know in chronic Lyme that there is an active infection still present. Well in the other scenario, what we will see is Laden infections. This idea that the organism is still surviving in our body but not causing tissue damage.

And this is, in fact, a model that medicine accepts readily because there are many, many opportunistic organisms that already live in the human body and don't cause us damage. In the last, we ended up getting an immune response to them, and some of the things we know of can be anything from pseudomonas to Proteus in the bowel or proprio bacteria that live on our skin.

And we don't have acne. You don't have inflammatory bowel diseases because we have Mikot back there. But these organisms are present in us. And so what I would say is that with relia persisting in our bodies, it's going to create difficulty with testing. A lot of testing right now is based on the idea of being able to recognize the presence of the organism.

And that can be through antibody mediated studies where you may find a  urinary PCR that's looking for the presence of DNA in a patient's urine. Well, if you have a latent infection, you have an organism surviving in the body in any of these numbers, these immune privilege sites, wherever, but actually not causing tissue damage, you will continue to see DNA present in low levels in these latent infections.

And in fact, the DNA can persist for extended periods of time, even following an active infection, meaning once you've been exposed to something, you're gonna have that DNA in your body. And one model we have for this, even if it's micro, which you see in women who've had children, that we can find the presence of fetal DNA from their child decades later in the central nervous system.

We know that it persists. And I would actually argue that as we find DNA and urine for a person who's had Lyme disease that it cannot distinguish between an active and a latent infection. In fact, many of these urinary PCR studies describe what's described as degraded DNA, and in  this antigenic shedding may only support the reality of presence rather than active and infections.

So again, I state here, antigenic shedding will continue at low levels, even in latent infections due to pathogen replication and turnover, natural breakdown of biofilm post cell apoptosis. Immune management and cellular and matrix detoxification of these proteins that we will continue to shed.  Proteins and DNA that can contribute to immune reactivity, but also, create false negatives on testing potentially. 

Here are a few studies that also show that antigenic debris or pieces of dead bacteria can persist following treatment. There's this concept of an Amber hypothesis, which states the pathogenesis of joint swelling in Lyme arthritis is due to the introduction into the joint space of non-viable spirochetes or more likely actual DNA or debris, a meshed host derived from a collagenous matrix. Just pieces of dead bacteria cause you were once infected and you killed it. And,now that's there and, it may be latent as well.

I really like this next statement that says the detection of spirochetes and nucleic acids does not necessarily correlate with the presence of intact metabolically active organisms. Other end points that focus on the persistence of Spire, actual components such as DNA and messenger RNA, although they have less direct importance to the issue of antibiotic efficacy, might be pertinent in explaining the persistence of inflammation in patients.

Now, that is a big, powerful statement, the idea that persistence of DNA and messenger RNA may not have much bearing at all to continuing antibiotics, but it can explain why people have persistent inflammation despite appropriate treatment. Let's take this idea of inflammation. as we start to consider the concept of inflammation in chronic inflammatory illness. I think the first thing we can take as a model is gender disparity. Patients who continue to experience chronic Lyme symptoms and have post-treatment Lyme syndrome are significantly more likely to be female than male. Well, it's interesting because this preponderance in women is also seen with other conditions like fibromyalgia, chronic fatigue syndrome, lupus, chemical sensitivity, inflammatory bowel diseases, rheumatoid arthritis, inflammatory illness, and other systemic  autoimmune diseases. What would explain this increased immune reactivity in women. There's likely a number of explanations for this, and certainly hormones in men have their own effects, but we know that estrogen suppresses TH1 dependent diseases, but it potentiates TH2 dependent diseases.

And this difference between the male and female immune system can suggest that there may be an increased immune reactivity in women that can predispose them to developing specific autoimmune diseases associated with those two responses. And this may have a natural evolutionary explanation because helper cytokines tend to have more of an anti inflammatory response.

And in the end, it may help in assisting with pregnancy and allowing a woman to prevent any immune concerns during a pregnancy. This may make a lot of sense, but it can also predispose to some autoimmune inflammatory problems, as we discussed, the idea of immune mediated inflammation in both chronic Lyme and post-treatment Lyme symptoms.

The question is, why is this so important? Well,  it's of critical importance because as a clinician trying to understand what to do with a person, this idea of looking at inflammation as it relates to immune reactivity can support your diagnostic assessment. You need to understand the spectrum between immune mediated inflammation and pathogen mediated tissue damage, because ultimately both of those roots can cause the same symptoms.

By understanding it can assist in decision making for treatment interventions it helps you as a clinician to create a balance between antimicrobial therapies and immune based therapies. It's a big spectrum between using an antibiotic and using something like low-dose immune therapy on the other side.

What are you going to do? Or there's a whole range of things in the middle. And ultimately this model can help to provide a context to better understand how to support long term healing and your patient. Do you want to balance their adaptive immune response by adding  support things that are going to increase the innate immune response and assist in removing intracellular infections and as you would in active infection, or do you want to try and reduce that TH to reactivity as you would see in a latent infection and these immune mediated inflammatory scenarios? Do you need help to quilt that or do you suspect that this has been a problem that's been chronic enough that there's autoimmune like phenomena or an autoimmune component and you need to consider the TH 17 and 10 immune components with the T regulatory system.

And start addressing the patient with more auto-immune targeted therapies. This is one of my favorite paragraphs here and it's a great paper to read, but it's the idea of linking inflammation between infection and chronic illness. And I'm going to read this. It states, inflammation drives many chronic conditions that are still classified as autoimmune or immune mediated.

Both the innate and adaptive immune responses play critical roles in the pathogenesis of these inflammatory syndromes. Therefore, inflammation is a clear link between infectious agents and chronic diseases. Aberrant cellular and humoral responses to infections can launch the continuum from infection to long term. This is a big jumping off point and establishes this link of inflammation. Let's start to look at what inflammatory markers are associated with post-treatment Lyme syndrome, chronic Lyme, and these inflammatory conditions.

One of these is a chemokine known as CCL 19. This is highly elevated in post-treatment Lyme syndrome. Now CCL 19 is a chemokine that functions to attract and position T cells, B cells and dendritic cells for immune response generation. It potentiates these guys and wakes them up and says, be on the alert.

Get ready to deal with whatever you find. It's this hyperactive immune response. It potentiates it. And these elevated CCL 19 levels can reflect ongoing immune driven reactions at sites distal to secondary lymphoid tissue. What does that mean? It means in the tissue, in the areas of dysfunction. When someone says, I'm always sore, I have this pain constantly, I'm always fatigued, these areas of my body are affected. This idea of CCL 19 can explain that because there may be some organism persisting in that area of the body or in that region, and it's driving this immune response because CCL 19 is potentiating the inflammatory reaction.

The CCL 19 can be considered an early predictive biomarker. And that is summed up with this statement. Individuals with ideally treated early Lyme disease, having a greater than 12 fold higher risk of developing post-treatment Lyme disease syndrome, 12 times higher. It's a huge amount. And that's if elevation by six or 12 months. If their CCL 19 level is higher than 111.67 P grams per mil at one month post treatment. That is a huge statement because can you imagine if we could do a simple test on any patient who gets Lyme disease and we could predict within a month of treatment whether they're going to go on to have symptoms, it could allow us to start treatment early on with immune interventions.

Unfortunately, the CCL 19 to my knowledge is not a commercially available lab test at this time, and it's only been done in university studies. Certainly if anyone out there listening has found a source for running CCL 19, please get ahold of me and let me know where that's being done.

Another very important marker is the cytokine interleukin 23  in post-treatment lines. The stimulation of what's known as our T H 17 T cells and it correlates with the development of post Lyme symptoms with a P value of less than 0.02. So highly correlative.

And this area study here shows that of the patients with detectable IL 23 levels 61% went on to develop post Lyme symptoms, and amazingly, every person with levels greater than 230 nanograms per mil went on to develop symptoms associated with post-treatment. It's that idea of continuing symptoms beyond six months, no matter what you do.

And so these are huge numbers between IL 23 and CCL 19 because they can tell you who's going to go on to have these problems. So what is the role of interleukin? IL 23 is involved in the differentiation of TH 17 cells and this differentiation is especially potentiated in the presence of TGF data.

IL 23 is produced by inflammatory macrophages, resident microglia, dendritic cells, and activated TH 17 cells themselves. So what potentiates TH 17 also produces IL 23 so it self-drives that. IL 23 has been described as a central cytokine involved in autoimmunity and is looked at as a highly promising treatment target for certain inflammatory diseases.

I L 23 is found in the skin of patients with psoriasis. It's identified in bowel walls and chronic inflammatory bowel diseases, and it's found in synovial membranes and patients with rheumatoid arthritis. There's a lot there directly in tissue. There's a medication Stelara, which I'm going to not try and pronounce the generic drug name for, which is an IL 23 and IL 12 inhibitor that's used effectively in the treatment of psoriasis and Crohn's. We know that by inhibiting IL 23, we can improve these autoimmune diseases. And while that might sound promising in Lyme disease, unfortunately, all IL 23 and IL 12 share a certain receptor dimmer that causes this medication to inhibit both things.

And I L 12 is actually involved in that one response needed for a cell mediated immunity. And the innate immune system that could lower the ability of our immune system to deal with active infections and in fact potentially contribute to a latent infection becoming active again. Probably not a good idea for Lyme patients.

Maybe one day they'll develop a medication that's very selected for around 23 until then, we'll continue to do what we do. Unregulated T H 17 T-cell reactivity promotes autoimmunity. Your aberrant T H 17 responses are implicated in many autoimmune conditions, including rheumatoid arthritis, inflammatory bowel, lupus, multiple sclerosis, encephalomyelitis, psoriasis, and type one diabetes.

So big deal here. And it's interesting because elevations in TH 17 associated immune reactivity and cytokines are correlated with many different central neurologic, autoimmune diseases. And one model here is  they did a knockout study on mice where they genetically prevented them from being able to produce, what they found is that these mice were not able to produce IL 17 without IL 23. They found that these IL 23 deficient mice had reduced inflammatory IL six and TNF levels. And in fact, when they injected these mice with proteolipid protein, which is a myelin antigen, used to induce experimental auto encephalitis that they were not able to do in these mice, they were unresponsive to the development of autoimmunity against their brain. Clearly, IL has a very central role in promoting an auto immune reaction against antigenic cross reactions. T H 17 activation of a naive T cell promotes inflammation and at the same time inhibits tissue repair.

There's a double whammy here that goes on. It's been found that T H 17 activates an inflammatory response induced by preexisting tissue injury. When you have ongoing inflammation and tissue, as you would see from these reactions as we described, and you get 17 involved It's going to amplify that response and continue to perpetuate it.

It's like adding gas to a fire. It's been shown that TH 17 is synergistic with other cytokines like TNF alpha  and  weeding to that chronic inflammatory process, and this is what I said about this double whammy because in addition to promoting and adding fuel to the fire and contributing to more inflammation, TH 17 activation is also associated with destruction of the extracellular matrix andinhibition of repair and production of extracellular matrix. As you're continuing that inflammatory response and breaking that tissue down in a routine way, whether it be in a joint space or some other region of the body, it's also preventing repair of that tissue.

You can see how a degenerative process can really progress rapidly with these TH 17 inflammatory reactions. The question is, what is the role of  borreliosis? And  I use the term Brelia as it's here because it describes the presence of the bacteria. We're not describing whether it's an active Lyme infection, a chronic Lyme, or a post treatment Lyme.

It's Borrelia. And as I see it, a high T eight 17 if they're seated immune response, which we know is often accompanied by the presence of auto antibodies. If we correlate those immune responses and those cytokines with chronic Lyme related symptoms, it could provide us with a new paradigm to understand and treat post infectious symptoms in patients.

Very big. Another indicator of infection, mediate and inflammation that those of us in functional medicine come about many times is TGF beta one.TGF beta one is a cytokine produced by many different cells and almost all white blood cells, including T regulatory cells. And it's used to regulate local inflammation.

And much of the confusion around TGF beta one comes from the fact that it's described in the literature as having both inflammatory and anti-inflammatory properties, and it's clearly associated with chronic inflammatory responses as it's described. High levels of TGF beta are associated with excessive tissue inflammation, and as I describe it, it's like the shutoff valve.

When inflammation gets too high in a certain area of our body or in certain regions enough so that it's damaging the tissue and threatening the host. You have a way of trying to reduce that inflammatory response to that tissue, and TGF beta is one of those things. As the body increases TGF beta one, it'll inhibit T cell proliferation as well as differentiation of naive T cells into TH1 or 2 specific responses, and this can reduce the inflammatory response in those tissues.

Unfortunately the other side of TDF data1 is that it also stimulates the systemic inflammatory response and likely immune autoimmune reactivity by activating T H 17 T cells. So cutting down on local inflammation is unfortunately increasing systemic inflammation.because of this dual property of TGF beta one.

I think of it as a contributor to the persistence of certain bacteria in a vicious inflammatory cycle. And how you can think of this is because of its impairment on T-cell differentiation, TGF beta one will decrease a TH1 risk. Oh, it's by inhibiting  an ILT to induce proliferation of T cells, and that one response is needed for that for reinforcing the innate immune response in dealing with intracellular infections, as you might see in a chronic Lyme condition where you have active organisms still there.

In addition, it has further immune suppressive effects on our innate immune system by exerting immune suppression on CD eight cytotoxic T cells as well as natural killer cell activity level. And that's something we see a lot of. We test NK cell function in my clinic. And most of the patients who have chronic Lyme or post-treatment Lyme,  it certainly correlates with TGF beta.

One will have very low levels and K cell function. They might have enough numbers, their CD 56 levels might look okay, but the function of those natural killer cells is, they're just lazy and they're not doing anything, and they're not functioning to eliminate in life cell membranes in these bacteria.

Ultimately. high TGF levels may be associated with reduced neurogenesis and a tilt towards antibody mediated immune inflammation, as well as contributing to cross-reactive autoimmune reactions.. I like this light a lot because it really sums up how TGF beta one contributes to this inflammatory genesis.

You can see here on the right side as you follow the CD four helper, naive T cell and red there, and you see the TGF beta one inhibiting what they described as anti-inflammatory T-cells, meaning differentiation of T-cells into TH1 or TH2 needed to stimulate an immune response. On the other side here, TGF beta one in the presence that synergism with IL can stimulate pro-inflammatory cells like T H 17, that can contribute to autoimmunity, as I mentioned, as well as B cell proliferation, which leads to that TH2  or you might say humeral dominant autoimmune response and and persistent inflammation. Another maybe little known or lesser known, marker that you will find in an inflammatory marker that you'll find in chronic Lyme. And then post-treatment Lyme is a part of the classical complement pathway, and has a role in establishing the continuum from persistent infection to chronic inflammation.

CFRA is described quite a lot in the literature on chronic inflammatory response, as Shoemaker describes for things like mold illness. Well, it's also described by stricter safely and chronic Lyme disease, especially those with predominant musculoskeletal symptoms. It's very high in those, in these patients, and not surprisingly,  is decreased in Lyme.

Patients who respond to antimicrobial therapy do well, you're going to your numbers.  It's also high in chronic fatigue syndrome and fibromyalgia. That brings up the question and likely they think that many of us know that probably there is some infectious etiology at the heart of fibromyalgia and chronic fatigue that's perpetuating this immune inflammatory response.

Another source of inflammation in the body are resident macrophages, microglia. Cause microglia stimulation will lead to central neurologic inflammation. Microglia are innate immune cells in the central nervous system that are stimulated by infections through toll like receptors. And FC receptors that detect a portion of the IgG antibody responses for certain antigen specific antibodies.

Chronic stimulation of microglia will drive pro-inflammatory profiles directly in the central nervous system in the brain. Tissue damage, neurodegeneration and chronic pain accompany neuro immune activation. Big deal. Cause you can get central pain syndrome, which means you can feel pain anywhere if you light the brain up on fire.

The neuroborreliosis symptoms, the presence of symptoms that we think of as neurologic and in chronic Lyme and post-treatment Lyme syndrome. Well, there's a lot of evidence that those symptoms are glial driven inflammatory symptoms. And, that is where the neurologic impairment comes from.

It is from our own immune system reacting. And we see that with upregulation of interleukin six, interleukin eight and TNF alpha. And this study, which is only about a little over a year old, it looks like here, I guess it's about 2018, incredible study, worth consideration. And I'm going to read the title of this study cause it's quite powerful. It's A Primary Human Microglia are Fager civically active and respond to Borrelia with upregulation of Kima kinds and cytokine. Why is that a big deal? Well in this study, they looked at the ability of Borrelia to drive wheel inflammation. And what they found is that both live Borrelia aspire, Keats, and interestingly dead organisms.

And what they found is that dead organisms and proteins from Borrelia, in fact were much stronger than the live spirochetes at actually activating microglia. The big deal because the dead things are actually having more of an inflammatory response in this case, and they're postulate here, is that the presence of Spire, actual debris in the central nervous system following antibiotics where you've got pieces of dead bacteria now and you can drive persistent inflammation in post-treatment Lymes. That sounds familiar, and like what you talked about earlier with this idea of persistent antigenic debris or DNA. Again, we're seeing more studies saying that this stuff can come and be trapped in the central nervous system as well as in peripheral tissue. So another source of ongoing inflammation is autoimmunity.

And we know that autoimmunity may drive persistent symptoms in chronic Lyme and post-treatment Lyme syndrome. We talked about with T H 17 right? And you end up pushing this inflammatory response far enough, and you actually can get a systemic autoimmune reaction. And this occurs as the literature clearly states, many times there's the idea of molecular mimicry that occurs due to cross-reactive antibodies from Barellia surface glycoproteins that look like other proteins in our body. And a quick search on some of these things. It was very, very easy to find a number of examples of this.  The LFA one protein is an auto antigen against OS pay reacted TH1 cells. The 31 KDA protein can cross react with LFA 1 and create treatment resistant Lyme arthritis.  

There has also been shown the presence of anti  antibodies and there are no Berlioz's or antibodies against axons.  Bergdorf writes specific IgM antibodies to flagellin cross-react with neuronal antigens. And in Lyme carditis they have actually found antibodies against alpha myosin suggesting that your heart, actually the cardiac muscle may be attacked secondary to an auto immune response.

Again, a lot of inflammation. Now that we've looked at inflammation as a common denominator and bacterial persistence, we need to deal with how we're gonna deal with the inflammation. How are we going to treat these patients? And there are a lot of Infor interventions that can be used to address immune modulation.

And now Trek zone is a incredibly important and powerful immune modulator that almost all of the patients I see with chronic Lyme and post-treatment Lyme ended up using because it helps in assisting with everything I talked about today. Naltrexone has both an opioid effect as well as a non-opiate effect.

And the opioid effect is that low-dose Naltrexone at doses to about 400 mil, 4.5 milligrams, binds to the mute opioid receptor and temporarily blocks those receptors. It's there for just a few hours, maybe up to about six hours. And that pulsatile effect has been shown to result in an increase in native endorphins in Kathleen's as well as the opioid receptor production  growth factor receptors.

We operate regulate those things. And why is that important? Endorphins do a lot of things. They enhance analgesia, they support mood, they keep our sex drive up. They keeip appetite up and contribute to overall sense of wellbeing. It's been shown that endorphins inhibit inhibit T-cell proliferation as well as B cell based antibody production.

Endorphins reduce proinflammatory cytokines while increasing immune regulation, and that's been shown by its ability to decrease TNF alpha. At levels of interleukin 10 which are associated with key regulatory cells or immune tolerance, and in Catlin's known as opioid growth factor it's been shown to promote tissue healing as well as regulating cell growth and abnormal cells. These are big deals.  Low dose naltrexone as a model for treating inflammatory diseases has shown established efficacy in a number of known inflammatory conditions. Low dose naltrexone has effectiveness on Crohn's disease, multiple sclerosis, chronic regional pain syndrome, and fibromyalgia.

And t's been shown to have some of these effects on inflammation by reducing cytokines that are known to promote no susception Alinea and hyperalgesia. Things. We've talked about I all six TNF alpha IL to IL 15 IL 17 the deal is here you're starting to see the full circle of the cytokines and how damaging they can be, and we've got this incredible medication that's readily and affordably available to our patients that can directly lower these levels.

What about the non opioid based anti-inflammatory effects of no tracks? Well, we talked about microglia and the effects that it can have on the central nervous system that can lead to pain almost anywhere in the body and contribute to immune dysfunction. Once again Now Trek on low dose naltrexone can inhibit signaling of toll-like receptors by pump recognition on microglia. It stops micro glial activation by preventing the toll-like receptors from recognizing those pathogen associated molecular patterns. And LDN is associated with attenuation of inflammatory cytokine production in the central nervous system. It reduces neuro inflammatory cytokines.

There's some common denominators here. You see IL six again, you'll see TNF alpha I L 12 NF Kappa B and TGF beta.  We talked about chronic stimulation of  receptors on microglia contributes to the Genesis and pathogenesis of multiple autoimmune diseases. We really want to keep those from being chronically stimulated.

Low dose naltrexone in the central nervous system can do a lot. It reduces chronic microglial activation, which can prevent neurodegeneration as well as preventing auto-immune progression and initiation. It reduces pain sensitivity, the Teague cognitive disturbances, sleep problems, mood disorders, and overall malaise.

And it's been shown to be neuroprotective to the central nervous system by reducing reactive oxygen species and preventing neuro chronic neuro excitation, like glutamate based neuro excitation. Low dose naltrexone and chronic inflammatory response and infectious illness or, even likely environmental illness as well (like mold is) probably something that needs to be talked about a lot more cause it has so many benefits. It modulates the immune system through endorphins and enkephalins. It reduces inflammation by inhibiting pro inflammatory cytokines. We know it directly down-regulates T H 17 and prevents autoimmune progression in Genesis, and it promotes tissue healing by stimulating met and Kathlyn levels, as well as upregulating opioid growth factor receptor production.

And chronic Lyme and post-treatment Lyme syndrome, Low dose Naltrexone has, as I summarize all of these effects, I conjecture on how that may be. It improves immune tolerance to a continuing antigenic presence. This is a big deal. If we accept the idea that we cannot eliminate this bacteria from our body, we need to learn to live with it.

We want to promote immune tolerance. We want that interleukin 10 and that T regulatory system to be working well and lowering things like TGF beta one and possibly CCL 19 might be a role in how that happens with LDN. It can reduce the likelihood of developing auto antibodies. Lowering the T H 17 response, reducing aisle 23 LDN can enhance.

Immune competency by balancing the TH1 and TH2 response so that you're not dominant on one of those or the other creating inflammation. Cause you can ultimately have inflammation by an overexpressed response on either branch of this immune arms. And we know that it reduces TGF aisle to aisle four, aisle 10 and TNF alpha, all things that can help modulate the immune system.

LDN can reduce neurologic and musculoskeletal pain and fatigue. We know that endorphins help enormously in this level. It's possible that by cutting down on  that might contribute. It can ameliorate neuro inflammatory symptoms, cutting down on IL six, TNF alpha, NF Kappa B. Those are things that are critical to cutting inflammation in the brain.

LDN can stimulate healing already damaged tissue. If you've had chronic Lyme and you get treated appropriately, you stop the pathogen mediated damage to the tissue, well, you still have had damage done that may need to be repaired. Your knees are still gonna hurt. If it's been eroded upon for years of infection, LDN can stimulate healing in those tissues through OGF in OGF receptors.

And again, the endorphins from LDN can result in improved mood, energy, sleep, and wellbeing. And it cannot be understated how important your mood is in dictating your immune system and your outcomes. supporting that can be a huge, huge factor. 

As we've talked today, clearly low dose naltrexone in both chronic and post-treatment Lyme syndrome is an incredible tool and something that I hope all the practitioners out there listening today will begin using in their own patients. I think you won't be disappointed, and I think that you'll find that it's incredibly synergistic with therapies, whether you're using antimicrobials in these chronic Lyme cases, or whether you're wanting to use other immune modulating therapies in these post-treatment cases, like low-dose immunotherapy or slit therapy or ozone or whatever else it's going to be.

Naltrexone is an important piece here. I want to thank everyone out there listening and I wanted to thank Linda today for asking me to speak on the uses of naltrexone in my own patients. It's been an honor and a pleasure to talk to you all today. Thank you very much. Bye.

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