How to Interpret Your CIRS Lab Results (TGF-β, MSH, C4a, MMP9, and VEGF Explained)
Imagine this: you’ve been sick for years. Fatigue that no amount of sleep fixes. Brain fog so heavy that simple tasks feel impossible. Pain that migrates from joints to muscles, then back again. You’ve gone from doctor to doctor, specialist to specialist. Each time, your bloodwork comes back normal.
- “Your thyroid is fine.”
- “Your cholesterol looks good.”
- “Your iron levels are in range.”
It’s just anxiety, depression, or stress. Well meaning practitioners suggest you to work on your gratitude practice. But deep down, you know something is very wrong…
This is the reality for many living with Chronic Inflammatory Response Syndrome (CIRS). Their suffering is real, but routine labs simply don’t capture what’s happening in their body. That’s why CIRS-specific labs like TGF-β1, MSH, and C4a are so critical. They look beyond surface-level numbers to reveal the hidden biology of chronic inflammation.
Why These Labs Matter in CIRS
CIRS is a multi-system, multi-symptom illness caused by exposure to biotoxins (from mold, Lyme, water-damaged buildings, and more). It affects the brain, immune system, hormones, and mitochondria. But unlike diabetes (with glucose) or hypothyroidism (with TSH), CIRS doesn’t have a single “yes or no” test.
Instead, it leaves a trail of immune and inflammatory markers. Among the most important are:
-
TGF-β1 (Transforming Growth Factor Beta-1)
-
MSH (Melanocyte Stimulating Hormone)
-
C4a (Complement Component 4a)
These labs offer objective evidence of the immune chaos CIRS creates.
TGF-β1 (Transforming Growth Factor Beta-1)
What it is:
A cytokine (signaling protein) that controls cell growth, immune function, and tissue repair. In healthy people, it keeps inflammation in check. In CIRS patients, it’s often excessively high, fueling widespread inflammation.
Reference ranges (Shoemaker protocol):
-
Normal: < 2,380 pg/mL
Why it matters:
-
Elevated TGF-β1 is linked to:
-
Asthma and airway inflammation
-
Fibrosis and tissue scarring
-
Neurological symptoms (brain fog, dizziness, mood changes)
-
-
In clinical practice, we often see patients with sky-high TGF-β1 who struggle with shortness of breath, migraines, and cognitive dysfunction.
Patient example:
A patient with recurrent “asthma” that didn’t respond to inhalers had a TGF-β1 over 12,000 pg/mL. Once CIRS treatment began, their lung function normalized—because the real issue wasn’t asthma, it was chronic inflammation.
MSH (Melanocyte Stimulating Hormone)
What it is:
A hormone made in the hypothalamus. It regulates sleep, pain perception, immune balance, and even gut integrity.
Reference ranges (Shoemaker protocol):
-
Normal: 35–81 pg/mL
-
Low: < 35 pg/mL (common in CIRS)
Why it matters:
Low MSH is one of the most characteristic findings in CIRS. It explains so many frustrating symptoms:
-
Chronic pain that doesn’t respond well to medication
-
Sleep disruption (patients wake unrefreshed or can’t fall asleep)
-
Increased infections like MARCoNS in the sinuses
-
Gut issues: food sensitivities, IBS, leaky gut
Clinical pearl:
When MSH stays low, patients often remain “stuck” in illness, even if other markers improve. Restoring balance here is critical for long-term recovery.
C4a (Complement Component 4a)
What it is:
Part of the complement cascade—your body’s innate immune defense. When biotoxins trigger the system, C4a is released in large amounts.
Reference ranges (Shoemaker protocol):
-
Normal: < 2,830 ng/mL
-
Elevated (suggestive of CIRS activity): > 2,830 ng/mL
Why it matters:
-
Elevated C4a signals immune overactivation.
-
Correlated with:
-
Profound fatigue
-
Cognitive dysfunction
-
Circulatory issues like cold hands/feet or unusual chest pain
-
Patient example:
One patient with constant ER visits for “cardiac pain” had normal heart scans—but their C4a was extremely high. Once CIRS treatment began, the chest pain resolved. This is a perfect example of how CIRS labs explain what conventional tests cannot.
MMP-9 (Matrix Metalloproteinase-9)
What it is:
MMP-9 is an enzyme involved in breaking down extracellular matrix and regulating tissue remodeling. It’s released by white blood cells during inflammation. In a healthy system, MMP-9 helps repair injury and fight infection. In CIRS, levels are often excessively elevated, signaling chronic inflammatory activity.
Reference range (Shoemaker protocol):
-
Normal: 85–332 ng/mL
-
Elevated (suggestive of CIRS activity): > 332 ng/mL
Why it matters in CIRS:
-
High MMP-9 reflects inflammatory cytokines leaking out of blood vessels into tissues, driving symptoms like:
-
Muscle and joint pain
-
Headaches and fatigue
-
Neurological issues (brain fog, irritability, mood swings)
-
-
Persistent elevation suggests ongoing vascular inflammation and poor control of the inflammatory cascade.
Clinical note:
Patients with elevated MMP-9 often present with diffuse pain that doesn’t match their imaging or physical exam. Lowering MMP-9 through targeted treatment often leads to noticeable relief in body pain and energy.
VEGF (Vascular Endothelial Growth Factor)
What it is:
VEGF is a protein that stimulates the growth of new blood vessels. It’s crucial for ensuring tissues receive enough oxygen during times of stress or activity. In CIRS, VEGF levels often swing to extremes. In some patients VEGF is too low. In others, it’s too high.
Reference range (Shoemaker protocol):
-
Normal: 31–86 pg/mL
-
Low (common in CIRS): < 31 pg/mL
-
High (less common, but seen in some cases): > 86 pg/mL
Why it matters in CIRS:
-
Low VEGF means poor blood vessel growth, leading to:
-
Exercise intolerance
-
Shortness of breath
-
Post-exertional malaise (worsening after activity)
-
-
High VEGF can contribute to abnormal vessel growth and inflammation, though this is less typical than low VEGF.
Clinical note:
Many patients with crushing fatigue after even mild exertion have abnormally low VEGF. Correcting underlying CIRS drivers can normalize VEGF and restore exercise capacity.
Why Most Doctors Miss These Labs
If you bring these results to a conventional doctor, they may say:
-
“TGF-β1? That’s used for transplant rejection or pulmonary fibrosis.”
-
“MSH? That’s a skin pigment hormone, not relevant here.”
-
“C4a? I don’t even order that.”
They’re not wrong in their training but they’re missing the bigger picture. In CIRS-literate care, these markers are the cornerstones of diagnosis and monitoring.
Using These Labs in Recovery
-
Diagnosis → Abnormal results confirm immune dysregulation consistent with CIRS.
-
Guidance → Each marker tells us which pathways need support.
-
Tracking progress → Improvement in these labs often matches clinical recovery.
-
Relapse prevention → Rising numbers may flag renewed exposure before symptoms explode.
FAQ: Interpreting CIRS Labs
Q: Can TGF-β1, MSH, or C4a diagnose CIRS on their own?
No. They’re part of a larger diagnostic framework including symptoms, history of exposure, and visual contrast sensitivity (VCS) testing.
Q: My labs are “normal” by standard ranges but abnormal by Shoemaker ranges. Which matters?
Shoemaker’s reference ranges are based on CIRS patient data and are much more sensitive for detecting illness. Standard labs often miss subtle dysfunction.
Q: Do these labs change quickly?
Some, like C4a, can fluctuate rapidly with exposure. Others, like MSH, may take months to improve. That’s why repeat testing is so important.
Q: What if my doctor dismisses these labs?
Unfortunately, most conventional providers are not trained in CIRS. Working with a CIRS-literate clinic ensures these results are properly understood and acted upon.
Why We Value These Labs at Flourish Clinic
At Flourish Clinic, these tests are indispensable. They:
-
Validate patient suffering with hard data.
-
Provide a roadmap for treatment.
-
Help us track real progress and spot relapse early.
For many patients, it’s the first time their illness is finally seen, explained, and measured.
What This Means For You
If you’re struggling with unexplained fatigue, brain fog, pain, or multisystem symptoms, don’t settle for “normal labs.” Understanding TGF-β1, MSH, C4a, MMP9, and VEGF could be the missing link to diagnosing and treating CIRS.