Myeloperoxidase (MPO) is an enzyme released primarily by neutrophils, the white blood cells that serve as the immune system’s first responders. Anything that activates or increases neutrophils tends to push MPO levels higher, which means the list of causes ranges from straightforward bacterial infections to chronic conditions like heart disease, autoimmune disorders, and lung disease. Elevated MPO is not a diagnosis on its own but a signal that neutrophil-driven inflammation is happening somewhere in the body, and understanding where that inflammation originates is the key to interpreting a high reading.
What MPO Actually Does
MPO is stored inside neutrophils in compartments called azurophilic granules. When neutrophils encounter bacteria or other threats, they release MPO along with hydrogen peroxide and chloride ions. MPO uses these ingredients to produce hypochlorous acid, the same active ingredient found in bleach, which is extraordinarily effective at killing microbes.1PubMed Central. Myeloperoxidase: Regulation of Neutrophil Function and Target for Therapy The enzyme also generates other reactive oxidants capable of modifying fats and proteins throughout the body.2PubMed. The reactions of hypochlorous acid, the reactive oxygen species produced by myeloperoxidase, with lipids This antimicrobial arsenal is essential for fighting infection, but when MPO activity becomes excessive or chronic, those same oxidants damage healthy tissue. That dual role explains why elevated MPO shows up across such a wide range of conditions.
Acute Infections
The most common and most transient cause of high MPO is a straightforward bacterial infection. When bacteria invade, the body floods the bloodstream with neutrophils, and those neutrophils degranulate, dumping MPO into both the infected tissue and the plasma. Studies tracking patients through acute bacterial infections have found that plasma MPO spikes at the start of infection and then drops back toward normal as the infection resolves.3PubMed Central. Neutrophilic granulocytes in acute bacterial infection. Sequential studies on lysozyme, myeloperoxidase and lactoferrin During sepsis, neutrophils also use MPO as part of a more dramatic defense mechanism: they extrude webs of DNA coated with antimicrobial proteins, including MPO, to trap pathogens. These structures, called neutrophil extracellular traps, are potent but come with collateral tissue damage.4PubMed Central. Reactive oxidants and myeloperoxidase and their involvement in neutrophil extracellular traps If your MPO came back high during an acute illness, the most likely explanation is simply that your immune system was doing its job. A recheck after recovery should show a return to baseline.
Heart Disease and Atherosclerosis
This is where elevated MPO starts to tell a more complicated story. MPO does not just fight germs; it actively contributes to the buildup of plaque inside arteries. The oxidants it produces chemically alter LDL cholesterol in ways that make it unrecognizable to the body’s normal cleanup receptors. Instead, immune cells called macrophages gobble up the modified LDL through scavenger receptors and become engorged “foam cells,” the hallmark of an atherosclerotic plaque.5PubMed Central. Myeloperoxidase: a potential therapeutic target for coronary artery disease MPO is consistently found within atherosclerotic lesions themselves.6PubMed Central. Role of myeloperoxidase in inflammation and atherosclerosis
MPO also damages blood vessels from the inside by interfering with nitric oxide, the molecule that keeps arteries relaxed and flexible. MPO both consumes nitric oxide directly and chemically disables the machinery cells use to produce it.5PubMed Central. Myeloperoxidase: a potential therapeutic target for coronary artery disease The result is stiffer, less responsive blood vessels, a condition known as endothelial dysfunction, that sets the stage for heart attacks and strokes.7PubMed. Myeloperoxidase and its contributory role in inflammatory vascular disease
These are not just laboratory observations. In patients admitted with acute coronary syndromes, elevated MPO predicted a roughly doubled risk of death over six months, and high MPO remained an independent risk predictor even after accounting for other markers like troponin and C-reactive protein.8PubMed. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes A meta-analysis pooling multiple studies confirmed that high MPO significantly predicted mortality in acute coronary syndrome patients, with about twice the odds of death compared to those with lower levels.9PubMed Central. Prognostic Role of Elevated Myeloperoxidase in Patients with Acute Coronary Syndrome: A Systemic Review and Meta-Analysis Particularly striking is that MPO identified patients at risk even when troponin, the standard heart-damage marker, was undetectable.8PubMed. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes
Chronic Lung Conditions
People with chronic obstructive pulmonary disease (COPD) tend to have persistently elevated MPO in their airways. The chronic inflammation that defines COPD drives a constant influx of neutrophils into the respiratory tract, and those neutrophils degranulate continuously. Sputum MPO levels in COPD patients track closely with the number of neutrophils present, essentially serving as a readout of how active the airway inflammation is.10PubMed Central. Sputum myeloperoxidase in chronic obstructive pulmonary disease MPO levels are elevated in both asthma and COPD compared to healthy lungs, but the increase is markedly more pronounced in COPD.11American Journal of Respiratory and Critical Care Medicine. Granulocyte Activation Markers in Induced Sputum: Comparison Between Chronic Obstructive Pulmonary Disease, Asthma, and Normal Subjects In COPD specifically, sputum MPO correlates with other inflammatory signals like interleukin-8, pointing to a self-reinforcing cycle in which inflamed tissue recruits more neutrophils, which dump more MPO, which damages more tissue.12PubMed. Airway inflammation in COPD assessed by sputum levels of interleukin-8
Inflammatory Bowel Disease
In the gut, MPO elevation shows up as a local phenomenon. Patients with Crohn’s disease and ulcerative colitis have higher fecal MPO levels than healthy individuals, and those levels climb in step with disease severity.13PubMed Central. Fecal Myeloperoxidase as a Biomarker for Inflammatory Bowel Disease Fecal MPO correlates well with what gastroenterologists see during endoscopy: the worse the visible inflammation, the higher the MPO.14PubMed Central. Myeloperoxidase Enzyme Activity in Feces Reflects Endoscopic Severity in Inflammatory Bowel Disease
This correlation is strong enough that fecal MPO is gaining traction as a clinical biomarker. One study found that patients with a baseline fecal MPO above a certain threshold were nearly four times as likely to experience a complicated disease course over the following year.15Journal of Crohn’s and Colitis. Faecal Myeloperoxidase as a Biomarker of Endoscopic Activity in Inflammatory Bowel Disease For people with IBD, a high MPO reading is less about discovering something new and more about gauging how active the disease is at a given moment, potentially without the discomfort of a colonoscopy.
Autoimmune Vasculitis
In a particularly destructive twist, the immune system can produce antibodies that specifically target MPO itself. These anti-MPO antibodies, a subtype of antineutrophil cytoplasmic antibodies (ANCA), are the defining feature of MPO-ANCA-associated vasculitis, a condition in which blood vessels throughout the body become inflamed and damaged. The antibodies latch onto MPO on the surface of neutrophils, triggering the cells to activate inappropriately. The neutrophils then attack blood vessel walls directly, leading to tissue damage in the kidneys, lungs, skin, and other organs.16The Lancet Rheumatology. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis The neutrophils become both the weapon and the target of the autoimmune response, degranulating their toxic contents into blood vessel walls and generating reactive oxygen species that compound the injury.17Advances in Anatomic Pathology. Pathophysiology of ANCA-associated Vasculitis In this context, elevated MPO in the blood reflects both the release from destroyed neutrophils and the ongoing autoimmune assault on blood vessels.
Smoking
Cigarette smoking is one of the most modifiable causes of chronically elevated MPO. Smokers carry higher total white cell and neutrophil counts than nonsmokers, and their individual neutrophils contain about twice the MPO content of a nonsmoker’s neutrophils. A study of chronic smokers found the MPO content of their circulating neutrophils was roughly double that of matched nonsmoking controls, reflecting chronic stimulation of the bone marrow to produce “hotter,” more primed immune cells.18European Respiratory Journal. The response of human bone marrow to chronic cigarette smoking Cigarette smoke also directly damages neutrophils in the lungs, causing them to release MPO and other inflammatory contents into the airways.19PubMed. Cigarette smoke-induced damage-associated molecular pattern release from necrotic neutrophils triggers proinflammatory mediator release This helps explain why smokers develop COPD at such high rates: the dual insult of more neutrophils with more MPO creates a relentless oxidative assault on lung tissue.
Exercise, Diet, and Obesity
Even a single bout of moderate exercise can temporarily bump MPO levels, because physical exertion activates neutrophils. One study found that 30 minutes of moderate-intensity exercise significantly increased plasma MPO in healthy people.20PubMed. Does acute exercise affect the susceptibility of low density lipoprotein to oxidation? This is a transient, normal physiological response and not a sign of disease. If you had blood drawn shortly after a workout, that alone could explain a mildly elevated result.
Diet plays a role too, at least in animal models. In mice prone to atherosclerosis, introducing a high-fat diet caused circulating MPO to spike sharply within weeks.21PubMed Central / AHA Journals. Accumulation of myeloperoxidase-positive neutrophils in atherosclerotic lesions in LDLR-/- mice While direct translation to human diets is limited, the finding fits with what we know about obesity and metabolic syndrome. In obese individuals, especially those with insulin resistance, the chronic low-grade inflammation driven by excess fat tissue keeps leukocytes in an activated state, leading to persistently elevated MPO.22PubMed Central. Association between Myeloperoxidase Levels and Risk of Insulin Resistance in Egyptian Obese Women Fat cells themselves produce inflammatory signaling molecules that interfere with insulin signaling and keep the immune system on a low simmer, which means elevated MPO in obesity is not just a marker but part of the machinery linking excess weight to cardiovascular disease.
Genetic Variation
Not everyone produces the same amount of MPO, even under identical conditions, and part of the difference is genetic. Variations in the gene encoding MPO influence how much enzyme a person’s neutrophils produce and release. Research has identified specific genetic variants where certain genotypes are linked to measurably lower or higher MPO levels. For instance, in patients with gestational hypertension, the genotype at one well-studied promoter region of the MPO gene significantly affected circulating MPO concentrations.23PubMed Central. Functional MPO Polymorphisms and Haplotypes Affect Both Myeloperoxidase Levels and Association with Hypertensive Disorders of Pregnancy
These genetic differences have real clinical consequences. A study constructed a genetic risk score from 15 common gene variants associated with higher MPO levels and found that people whose genetics predisposed them to elevated MPO had increased risk of both hemorrhagic and lacunar stroke, directly implicating the MPO pathway in cerebral small vessel disease.24PubMed Central. Genetic variants influencing elevated myeloperoxidase levels increase risk of stroke In other words, some people are essentially running hotter MPO levels throughout their lives because of their DNA, and that baseline difference appears to contribute to vascular disease risk.
Medications That Trigger MPO-Related Problems
Certain drugs can indirectly raise MPO activity or, more dramatically, trigger the immune system to produce antibodies against MPO. Drug-induced ANCA-associated vasculitis has been linked to medications including hydralazine (used for high blood pressure), propylthiouracil (used for overactive thyroid), levamisole (an antiparasitic sometimes found as a contaminant in illicit cocaine), and immune checkpoint inhibitors used in cancer therapy. The mechanism appears to involve enhanced formation of neutrophil extracellular traps, which expose MPO to the immune system in ways that can break immune tolerance and provoke autoantibody production.25PubMed. Drug- and vaccine induced ANCA-associated vasculitis: An overview While proving that a specific drug caused vasculitis in an individual patient is difficult, the pattern has been documented enough that clinicians are advised to consider medication-related causes when ANCA vasculitis develops in a patient on one of these drugs.
Kidney Disease
The kidneys are frequent casualties of MPO-mediated inflammation, in part because they are a common target organ in ANCA-associated vasculitis. But the relationship runs in both directions. Chronic kidney disease itself creates conditions that promote elevated MPO: the buildup of uremic toxins and the chronic inflammatory state that accompanies declining kidney function keep neutrophils in a primed and activated state, generating oxidative stress that further damages kidney tissue and blood vessels.26PubMed Central. Role of Myeloperoxidase in Patients with Chronic Kidney Disease This creates a vicious cycle: kidney disease raises MPO, and MPO-driven oxidative damage worsens kidney function and accelerates the cardiovascular disease that is the leading cause of death in kidney patients.
MPO in the Brain
An area of growing research interest is the role of MPO in neurodegenerative disease, particularly Alzheimer’s. MPO has been found co-localizing with the amyloid plaques that are a hallmark of Alzheimer’s disease.27PubMed. Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer’s disease Activated microglia, the brain’s resident immune cells, express MPO in Alzheimer’s brains.28PubMed. Neuronal expression of myeloperoxidase is increased in Alzheimer’s disease More recent work has shown that neutrophils from the bloodstream can infiltrate brain tissue in Alzheimer’s, and these infiltrating neutrophils deposit MPO around amyloid plaques.29PubMed Central. Neutrophil-vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer’s disease Whether MPO is merely present as a bystander or actively contributing to neuronal damage is still being worked out, but the oxidative environment it creates could plausibly worsen the tissue damage around plaques.
Why Specimen Handling Matters for Your Test Results
If you have had an MPO blood test, it is worth knowing that the result is surprisingly sensitive to how the sample was handled. Neutrophils continue to release MPO after blood is drawn, especially at room temperature. Research developing clinical MPO assays found that heparinized whole blood must be kept on ice before centrifugation to prevent this ongoing release, and that serum samples are not recommended for MPO measurement because the clotting process itself activates neutrophils and artificially raises levels.30PubMed. Development of an ELISA for myeloperoxidase on microplate: normal reference values and effect of temperature on specimen preparation A sample that sat at room temperature before processing could yield a falsely elevated reading. If your result seems unexpectedly high, especially in the absence of symptoms that would explain it, asking whether the sample was handled under cold conditions is a reasonable question for your lab.
Emerging Therapies Targeting MPO
Given MPO’s role in driving vascular inflammation and tissue damage, pharmaceutical companies have begun developing drugs that specifically inhibit the enzyme. One such compound, AZD4831, targets extracellular MPO and has shown the ability to decrease inflammation and improve microvascular function in preclinical models. It has progressed into clinical trials for heart failure with preserved ejection fraction, a condition where chronic microvascular inflammation is thought to play a central role.31PubMed. Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results The idea is not to eliminate MPO entirely, since it is genuinely needed for fighting infections, but to dial back the excess activity that damages blood vessels and organs in chronic disease. Whether these drugs will prove effective enough to reach routine clinical use remains to be seen, but the fact that they exist at all underscores how seriously researchers take MPO’s contribution to disease beyond its original job description as a microbial killer.