CIRS Blood Markers and Treatment

Chronic Inflammatory Response Syndrome (CIRS) is a multifaceted condition characterized by a range of symptoms and underlying biological markers that can be detected through blood tests. Understanding these CIRS blood markers is crucial for both diagnosing the condition and monitoring treatment progress, particularly when following the Shoemaker Protocol.

 

Let’s explore the key blood markers associated with CIRS, how they help in diagnosing the condition, and their role in guiding treatment decisions. Additionally, we will discuss various treatment options available to correct abnormalities found in these markers, offering insight into the comprehensive management strategies that are essential for those affected by CIRS.

 

By taking a closer look into the specifics of blood markers and their correction, patients can more effectively navigate the challenges of treating and managing CIRS.

 

What Is CIRS?

 

 

CIRS is identified as a complex medical condition marked by extensive inflammation and a broad range of symptoms affecting various organ systems, due to an overactive immune response. Diagnosing CIRS accurately involves a thorough review of the patient’s medical history alongside specialized laboratory tests. The symptoms associated with CIRS can differ significantly from one person to another, which frequently results in either misdiagnosis or incorrect treatment. A significant challenge in identifying CIRS lies in its non-detection through conventional autoimmune blood tests, thus requiring specific diagnostic methods for accurate identification of the condition.

 

 

What are the primary factors that ignite the severe immune reactions and widespread inflammation seen in CIRS? The leading causes are biotoxins—natural toxic substances with distinct molecular weights that originate from various sources:

 

• Water-damaged environments: Around 80% of CIRS cases are linked to exposure to air in environments compromised by water damage, teeming with mold mycotoxins, bacteria, and a slew of chemical irritants. These contaminants trigger robust inflammatory reactions in individuals susceptible to CIRS, with both active and inactive mold components contributing to significant inflammation throughout the body and brain.

 

• Insect bites: Bites from specific ticks and spiders may cause ongoing health issues such as chronic Lyme disease, which are brought on by pathogens including Borrelia burgdorferi and Babesia microti. Additionally, toxins from recluse spider bites can cause long-lasting health effects.

 

• Seafood consumption: Eating tropical reef fish contaminated with ciguatera toxin, often associated with Pfiesteria and harmful algae blooms, such as cyanobacteria (blue-green algae), can lead to biotoxin-related health problems. These toxins build up as larger reef fish prey on smaller fish that have consumed dinoflagellates.

 

• Contact with contaminated water: Coming into contact with or inhaling water contaminated with toxic algae blooms, like Pfiesteria and cyanobacteria, can set off the inflammatory responses typical of CIRS.

 

• Other biotoxin sources: CIRS can also be triggered by exposure to certain vaccines, viruses, volatile organic compounds (VOCs), endotoxins, and actinomycetes, adding further to the body’s burden of biotoxins.

 

 

Due to their small molecular size, biotoxins can infiltrate cell membranes, making them difficult to detect in standard blood tests. These toxins typically enter the body through inhalation, although they can also be absorbed through ingestion, tick and spider bites, and direct contact with contaminated water.

 

Not all exposure to common biotoxins such as mold automatically results in CIRS; factors such as an individual’s genetic makeup and life stressors significantly influence their susceptibility to biotoxin-related conditions. Life events like severe illnesses, surgical interventions, high fevers, pregnancies, significant biotoxin exposures, and other traumatic incidents can provoke a cytokine storm. This immune reaction may activate the CIRS gene in those who are genetically prone, particularly in individuals with HLA-DR genes, suggesting that CIRS can arise at any point in life. Notably, the lack of symptoms does not mean one is immune, making genetic testing a vital component of preventive strategies.

 

While biotoxins may cause immediate sickness, most people’s immune systems are capable of detecting and eliminating these toxins efficiently. However, for those with a genetic predisposition to CIRS, their immune systems fail to recognize and clear these toxins, leading to their buildup in the body. This accumulation triggers a persistent, intense immune response and widespread inflammation, resulting in a variety of symptoms and chronic health issues.

 

The biotoxin pathway explains why CIRS is a multi-system, multi-symptom condition, you can learn more about the biotoxin pathway here.

 

For a more detailed understanding of CIRS, click here.

 

What Are the CIRS Blood Markers?

 

 

The first lab test needed is the HLA-DR which identifies the genetic susceptibility to CIRS. Please note, it is extremely rare to have CIRS if you do not have the haplotype. However, about 5% of CIRS cases are not in genetically-susceptible individuals. Working with a professional CIRS provider is best to help navigate this scenario in order to get proper treatment. HLA testing only needs to be completed once as a part of the CIRS diagnostic criteria.

 

In addition to the HLA-DR genetic testing, blood work for specific markers will be needed. These specific labs will be used for both diagnosis and monitoring clinical progress for CIRS. Be aware that different labs have different ranges for blood markers, making it important to have a trusted CIRS practitioner evaluate your results.

 

• MSH: Often referred to as the “master gland,” Melanocyte Stimulating Hormone (MSH) plays a critical role in regulating various hormonal and anti-inflammatory processes. It is observed that over 95% of individuals with CIRS exhibit low levels of MSH, a condition often influenced by the biotoxin pathway. This reduction in MSH heightens their sensitivity to mold toxins and can lead to a range of issues including sleep disturbances, gastrointestinal problems, mood fluctuations, hormonal imbalances, and other health concerns.

 

• TGF Beta-1: This crucial biomarker is essential in managing the innate immune system. The multifunctional protein is involved in regulating immune functions, cell survival, and cell migration. Elevated levels of Transforming Growth Factor Beta-1 (TGF Beta-1) are associated with a variety of health issues, including autoimmune disorders, neurological conditions, and other systemic complications.

 

• Complement C4a: C4a, a component of the complement system mentioned earlier, serves as a pivotal inflammatory marker for both diagnosing and monitoring CIRS. It reflects the innate immune response in individuals who have been exposed to water-damaged environments. This marker typically rises within 12 hours following acute exposure. During the treatment process, levels of C4a are observed to decrease rapidly once the individual is no longer exposed to the harmful environment.

 

• MMP-9: This enzyme plays a critical role in the breakdown of disease and various tissues under normal physiological conditions. Elevated levels of matrix metalloproteinase-9 (MMP-9) contribute to tissue damage within the walls of blood vessels, which in turn can cause inflammation in the brain, lungs, muscles, joints, and peripheral nerves.

 

• VEGF: VEGF, or Vascular Endothelial Growth Factor, is crucial for promoting the growth of new blood vessels, enhancing blood circulation, and facilitating the delivery of oxygen and nutrients throughout the body. When VEGF levels are diminished, it can result in insufficient blood flow and cellular deprivation, which are significant and frequent complications associated with CIRS.

 

• VIP: Vasoactive Intestinal Polypeptide (VIP) is a neuropeptide crucial for controlling cytokine responses, managing pulmonary artery pressures, and moderating inflammation throughout the body. Patients with CIRS commonly exhibit low levels of VIP, which can cause symptoms such as shortness of breath during physical activity and contribute to conditions such as diarrhea. VIP functions similarly to MSH in its regulatory effects on inflammatory processes.

 

Many other blood markers often become dysregulated by CIRS. Additional markers are usually tested initially to get a better understanding of all the downstream impacts caused by chronic, systemic inflammation. They may be tracked throughout treatment as well for resolution. You can learn more about some of these other impacted blood markers here.

 

However, these are the necessary markers needed for diagnosis and are more commonly tracked throughout treatment.

 

Pro-Tip: Always track VCS and symptom clusters. Your symptoms should dictate a lot of treatment. We don’t recommend just chasing numbers on blood work. Testing blood markers every three to four months is ideal but often varies from case to case.

 

Correcting CIRS Markers

 

 

The Shoemaker Protocol is designed to correct these abnormal markers in CIRS patients. While certain steps can be more impacted for normalizing particular markers, others may need additional support. Let’s take a closer look at some of the treatments available for correcting the key CIRS blood markers above.

 

MSH

The release of this neuroregulatory hormone is controlled by leptin in the pituitary. With CIRS, disruption of the leptin receptor from an increase in cytokines causes a drop in MSH, a master controller of many functions in the body. Low levels of MSH lead to dysregulation of multiple processes, causing:

 

• Problems with sleep patterns and melatonin, leading to disturbed sleep
• Problems with salt and water balance through its interaction with antidiuretic hormone (ADH)/arginine vasopressin (AVP) and serum osmolality, leading to increased thirst and urination, heart palpitations, and POTS
• Dysregulation of the immune system with increased inflammatory cytokines, T-cell abnormalities, and an increase in autoimmunity
• Increased pain due to decreased endorphin production
• Issues with increased gut permeability
• Reduction in androgens/low testosterone
• Colonization of the nose with MARCoNS
• Weight gain that’s unresponsive to changes in diet and exercise due to leptin dysregulation

 

Vasoactive Intestinal Peptide (VIP) is a peptide hormone that exerts a profound anti-inflammatory and immunomodulatory effect. Low VIP levels are commonly observed across CIRS patients as one of the downstream effects of the biotoxin pathway. As the last step of the Shoemaker Protocol, VIP Intranasal Spray can help correct low MSH levels.

 

Theoretically, there may be some natural treatment options for boosting low MSH levels. These treatments have yet to be fully researched but may be considered as additional supportive levers. These natural options and potential alternatives to VIP Intranasal Spray can be found in our CIRS Support Group.

 

Pro-Tip: Low-dose VIP may be used during different parts of the Shoemaker Protocol to help sensitive patients better tolerate binders, treating MARCoNS, or other potential roadblocks experienced in treatment. Some food sensitivities can be improved with diluted VIP. VIP can flare histamines, making it important to speak with your trusted CIRS practitioner if you struggle with histamine or mast cell activation issues. For individuals starting VIP as the last step of the Shoemaker Protocol, you must pass the following criteria: 1) MARCoNS must be eradicated, 2) pass the VCS test, 3) lipase is normal, and 4) must be out of exposure.

 

TGF-Beta 1

Elevated TGF Beta-1 indicates an overactive immune response and is a key marker for CIRS. It can change regulatory T cells into pathologic T cells, further driving inflammation. It may also cause tissue remodeling in multiple tissues in the body. Correcting TGF Beta-1 is important due to the potential for long-term tissue changes.

 

It is important to note that many various factors can cause elevated TGF Beta-1 outside of CIRS. Blood markers should always be interpreted together along with the specific context of each patient’s case.

 

In some cases, TGF Beta-1 will normalize on its own once a CIRS patient is out of exposure and on Cholestyramine (CSM) or Welchol, the prescription binders for CIRS, for an adequate amount of time. If TGF Beta-1 has not corrected on its own, step 10 of the Shoemaker Protocol addresses this. The final step of the Shoemaker Protocol utilizes Vasoactive Intestinal Peptide (VIP) Intranasal Spray which can also help correct elevated TGF Beta-1.

 

We recommend trying natural support options for correcting TGF Beta-1 first before trying the prescription option called Losartan. For a comprehensive list of natural supports and their specific protocols, please join our CIRS Support Group. Always work with your trusted CIRS practitioner to create the best-personalized treatment protocol for your case.

 

Complement C4a

The activation of the complement system plays an important role in our natural ability to ward off infection in addition to the pathogenesis of infection and inflammation. The complement cascade activation results in the formation of complement split products C3a, C4a, and C5a.

 

Complement C4a levels can become increased in any condition associated with inflammation. There are three general pathways by which the body increases C4a: the alternative pathway, the lectin pathway, and the classical pathway. These pathways are activated by infections, including bacteria, fungi, viruses, and parasites. Immunoglobulins (IgG, IgM) and C-reactive protein (CRP) can also increase C4a.

 

C4a appears to be an immune marker with elevated levels in the following disorders:

• CIRS
• Lyme disease
• Chronic Fatigue Syndrome
• Psoriasis
• Eczema
• Antiphospholipid syndrome
• Lupus (low levels of C4a)
• AIDS
• Schizophrenia
• Acute pancreatitis

 

Similar to TGF Beta-1, C4a may also correct on its own. In the context of CIRS, C4a can be directly tied to biotoxin exposure. Having C4a levels normalize during the Shoemaker Protocol can often indicate that the patient is out of exposure.

 

In addition to getting out of exposure and managing excess histamines, VIP Intranasal Spray during the last step of the Shoemaker Protocol can also help correct elevated C4a levels. Daily movement, high-quality fish oils, and specialized pro-resolving mediators (SPMs) are additional natural supports for helping reduce elevated C4a.