Stages of illness and recovery

According to the Marshall PathogenesisA description for how chronic inflammatory diseases originate and develop., chronic inflammatory diseases originate and develop when pathogens suppress the immune response. The immune response is regulated by nuclear receptorsIntracellular receptor proteins that bind to hydrophobic signal molecules (such as steroid and thyroid hormones) or intracellular metabolites and are thus activated to bind to specific DNA sequences which affect transcription., proteins attached to the nucleus of the cell. These nuclear receptors are activated by signaling molecules. As far as immune function is concerned, one of the key nuclear receptors is the Vitamin D ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response., which is located in many human cells especially immune cells. When active, the Vitamin D Receptor creates the instructions for proteins that comprise the innate immune responseThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease., the body's first line of defense against pathogens. The VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response. codes for hundreds, perhaps even tens of thousands of different genes. These include everything from genes that suppress tumors to those that code for the antimicrobial peptidesBody’s naturally produced broad-spectrum antibacterials which target pathogens., the body's natural broad-spectrum antibiotics.

This article reviews the different stage of illness and recovery for patients struck by chronic inflammatory disease. A description of many of the terms used here and in the Knowledge Base is contained in the glossary.

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Prior to immune dysfunction

In a healthy human, the body can carefully regulate activity of the VDR, which it does by controlling the concentrations of two key forms of vitamin D: 25-DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver. and 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol.. Both molecules are attracted to the Receptor and bind to it for hours at a time, after which they drop off. The essential difference between the key molecules is that when 1,25-D docks to the VDR, it turns the Receptor on; when 25-D docks to the VDR, it is turned off. When it becomes necessary to turn on the VDR, the body increases production of 1,25-D. Conversely, when an active VDR is no longer necessary, the body converts 1,25-D into 25-D. In healthy humans, this control mechanism works well. For example, in the event a pathogen is noticed, the body increases production of 1,25-D, which in turn increases activity of the VDR.

Process of immune system dysregulation

Multiple pathogens including bacteria such as “gliding” biofilm A structured community of microorganisms encapsulated within a self-developed protective matrix and living together. bacteria and Mycobacterium tuberculosis as well as viruses such as Epstein-Barr and HIV have discovered a way to persist and reproduce by inactivating the VDR. In the case of the gliding biofilm bacteria, some species produce a protein called Capnine which has an effect similar to 25-D, in that it has an affinity for the VDR, but does not turn it on.

The body responds by increasing production of 1,25-D. While some 1,25-D activates the VDR, a lot does not, because the VDR is blocked by bacterial ligands and the body is never able to completely out-compete the production of bacterial substances.

The increase in 1,25-D introduces a new problem entirely. When 1,25-D reaches higher and higher levels, it begins to interfere with important activities of other nuclear receptors. While 1,25-D is the activating hormone for the VDR, at high enough levels it binds to and inactivates other receptors. Like the VDR, these receptors have a role in innate immune function, but they also transcribe genes that lead to production of hormones of their own such as thyroid hormones and the sex hormones. This is why high levels of 1,25-D can lead to low levels of other hormones.

Olmesartan Medoxomil partially activates the VDR

The Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP) is designed to interrupt the inflammatory disease process. The most important medication Marshall Protocol patients take is not the low doses of antibiotics, but the Benicar. MP patients take 40mg of Benicar – also known by its substance name, olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. – every four to six hours. At that dose, Benicar leaks into the cell where it begins to compete for the VDR. Like 1,25-D, Benicar turns on the VDR, but unlike 1,25-D, it does not interfere with the activity of the body's other nuclear receptors.

When activated by Benicar, the VDR begins transcribing the genes for proteins which comprise the innate immune response. With a stronger immune response, the body is more effective at killing pathogens including human cells infected by pathogens. When pathogens are destroyed, endotoxins are released and inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. is generated, both of which lead to symptoms of what is known as immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed..

Immunopathology, also known as the bacterial die-off reaction, is the temporary increase in the symptoms of disease. In Stage Three, immunopathology is a self-limiting reaction. The production of inflammatory signaling molecules called cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. prevents the immune system from targeting all pathogens at once.

It should be noted that Benicar has a second action, that of an anti-inflammatory. That is why many patients report feeling better when taking Benicar.

Continuing treatment, Olmesartan Medoxomil and 1,25 successfully reactivate immune functions

In Stage 4, the combination of Benicar and 1,25-D is entirely successful at displacing bacterial proteins such as Capnine. Patients would be able to slow their immune response by withdrawing Benicar. Choosing to do so, however, would reduce its anti-inflammatory, palliative effect, and depending on the load of stressors (exposure to pathogenic microbes, other environmental stressors, psychological stress, sleep deprivation etc) it is possible that microbes again may get a stronghold in the body. At this point, patients taking antibiotics will want to discontinue them, or at least adjust dosing so as to maintain tolerable immunopathologyA state in which a patient has maintained an acceptable intensity of bacterial die-off reaction. The primary goal of the Marshall Protocol.. Rather than a sign of failure, this is just a sign that the immune system is becoming healthy.

At the next stage VDR is self-sustaining, there will be widespread pathogen die-off

In Stage Five, the immune system becomes self-sustaining, and is fully able to combat chronic pathogens without antibiotics and even without Benicar. Benicar continues to be used, however, for its previously mentioned anti-inflammatory effect. At this point, vitamin D from ingestion or light exposure may be converted into 1,25-D, which now can drive the immune response since the vitamin D receptors are no longer blocked by bacterial ligands. For this reason, MP patients must be careful about exposing themselves to large amounts of light or sunshine.

Return to healthy VDR, new pathogens eradicated if they become significant

Stage 6 is like Stage 1, because the immune response is fully functional. Patients can wean or discontinue Benicar and even take in a reasonable amount of light.

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