Monocytes are the largest of all white blood cells and play an important role in the defense against germs and in inflammation. Read on to learn about these cells, the health effects of having higher or lower levels of monocytes, and how to keep your monocytes in a normal range.

Monocytes also play a role in controlling and mitigating the effects of Th1/Th2/Th17 dominance, which is an important factor in chronic inflammation, leaky gut, and more.

What are Monocytes?

Monocytes are the largest type of white blood cell. Approximately 2 to 10% of white blood cells are monocytes [1].

These immune cells circulate in the blood for several days before they enter the tissues, where they become macrophages or dendritic cells [12].

Monocytes protect against viral, bacterial, fungal, and protozoal infections [3].

These cells kill microorganisms, ingest foreign particles, remove dead cells, and boost immune responses [142].

However, they can also be involved in the development of several inflammatory diseases, including arthritis and atherosclerosis [5, 6, 7].

Monocyte Production in the Body

In adults, blood cells are produced mainly in the bone marrow.

All blood cells originate from common parent cells called hematopoietic stem cells [8].

The process of monocyte production is called myelopoiesis [9].

Factors that control this process are:

  • Transcription factor SPI1 [10111213].
  • Cytokines: SCF (stem cell factor), GM-CSF (granulocyte-macrophage-colony-stimulating factor), M-CSF (macrophage colony-stimulating factor, CSF1), IL-3, IL-6, and IFN-gamma [14151617].

After Monocytes Fulfill Their Job, What Happens Next?

Monocytes live for an average of 3 days before undergoing apoptosis (programmed cell death) [18].

Monocytes live longer when there is inflammation. Once inflammation resolves, cell death occurs [18, 19].

Normal Monocytes Reference Ranges

The normal range for Monocytes are:

  • 0.2 – 0.8 x10^9/L
  • 200 – 800 / microL
  • 1 – 10%

Having an optimal monocyte count means you have a lower risk of:

  • Viral, bacterial, and fungal infections [20]
  • Heart Disease [21]
  • Obesity [22]
  • Diabetes [22]
  • Death (mortality) [23]
Other Suggested Marker Tests if your monocytes are out of the optimal range:

White blood cell count, neutrophils, eosinophils, lymphocytes, and basophils.

High Levels of Monocytes (Monocytosis)

In monocytosis, the number of monocytes circulating in the blood is increased to more than 0.8×109/L in adults.

Conditions Associated with Monocytosis

  • Blood disorders (myelodysplastic disorder, acute monocytic, chronic myelomonocytic leukemia, Hodgkin and non-Hodgkin lymphoma) [242526]
  • Infections (tuberculosis, viral infections, bacterial endocarditis, brucellosis, malaria, syphilis) [272829303132]
  • Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease) [333435]
  • Sarcoidosis [36]
  • Cancers (ovary, breast, rectum) [2737]
  • Heart attack [2738]
  • Appendicitis [39]
  • HIV infection [2740]
  • Depression [41]
  • Childbirth [4243]
  • Obesity [44]
  • Severe pneumonia [45]
  • Alcoholic liver disease [46]

Health Effects of Elevated Levels

The condition of having high monocyte levels is known as monocytosis. This most commonly occurs during- and after chronic inflammation or infection [23].

However, there are also several other conditions that can be associated with monocytosis, such as heart disease, depression, diabetes, and obesity [21, 22, 47].

Monocytosis has been associated with a greater risk of death (mortality) from any cause [23].

The main causes of high monocyte levels are:

  • Chronic (long-term) inflammation [23]
  • Infections, such as tuberculosis, malaria, and syphilis [48, 49, 50]

High monocyte levels may also be caused by:

  • Autoimmune diseases, such as lupus, rheumatoid arthritis, and IBD [35, 33, 34]
  • Leukemias, such as chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia [51, 52]
  • Cancer [53]
  • Depression [41]
  • Obesity [54]

There are rarely any symptoms that go along with monocytosis itself. Instead, the symptoms mostly come from the diseases associated with monocytosis [22]. These symptoms include:

  • Inflammation [22]
  • Fever [55]
  • Pain [56]
  • Swelling [55]

1) Increase the Risk of Atherosclerosis

Monocytes and macrophages are essential to the development and exacerbation of atherosclerosis (hardening of the arteries) that can lead to heart attack, stroke, and heart failure [57].

Monocytes accumulate in blood vessels and contribute to the development and rupture of atherosclerotic plaques that cause blockage in blood vessels [58, 5960].

As hardening of the arteries progresses, the number of monocytes in the blood rises [61].

2) May Increase Inflammation in Diabetes

A clinical study showed no effect of diabetes on the number of circulating white blood cells, but monocytes were significantly increased [62].

Monocytes may induce inflammation in diabetes.

Studies showed that monocytes secrete increased levels of TNF-alpha, IL-6, and IL-1 in both type 2 and type 1 diabetic patients [636465666768].

3) Associated with Increased Risk of Death in the Elderly

An increased number of monocytes is associated with an increased risk of cardiovascular and cancer-related risk of dying in the elderly [23].

4) Facilitate Healing Process After a Heart Attack

After a heart attack, monocytes aid in the removal of damaged and dead heart cells, and in healing heart attack damage [6970].

Ways to Decrease Levels

1) Regular Exercise

Regular exercise is anti-inflammatory. Monocytes significantly decreased after a 6-week course of moderate intensity cycling in overweight sedentary women.

Monocyte counts were also significantly associated with reduced triglyceride levels, increased insulin sensitivity, and decreased body mass index [71].

2) Weight Loss

In obese people, weight loss was accompanied by a significant reduction in monocyte and neutrophil counts. The decrease in circulating monocytes correlated with better insulin sensitivity [44]. 

3) Omega-3 Fatty Acids

Regular consumption of omega-3 fatty acids, found in fish such as mackerel and salmon or fish oil supplements, may protect against atherosclerosis and heart disease [72].

People taking fish oil supplements were less likely to have inflammation in the blood vessel walls caused by monocytes. This effect was not as pronounced in people already taking medication to treat peripheral artery disease [73].

4) Mediterranean Diet

The Mediterranean diet may protect against inflammation caused by monocytes [74, 75].

The Mediterranean diet is comprised of foods such as seeds, nuts, vegetables, fruits, whole grains, and monounsaturated fats from olive oil.

5) Moderate Alcohol Intake

Alcohol influences monocyte function [76].

Studies suggest that acute alcohol consumption decreases inflammation in response to LPS in the gut [77].

Moderate alcohol consumption, about 1 or 2 drinks per day, significantly reduced monocyte production of inflammatory cytokines TNF-alpha and IL-1beta and increased IL-10 production [7877].

These mechanisms may contribute to the beneficial effects of moderate alcohol use on atherosclerosis.

Factors That Decrease Monocytes

1) Cortisol and Glucocorticoids

A single dose of cortisol decreased monocytes by 90% at 4 to 6 hours after treatment. This reduction persisted for about 24 hours. Subsequently, monocyte levels returned to normal 24 to 72 hours after treatment [79].

This decrease is thought to be a consequence of the redistribution of monocytes.

2) Estrogen and Progesterone

Estrogen, and possibly also progesterone, decrease monocyte count. This could explain the decreased functioning of cell-mediated immunity during pregnancy [80].

3) Infliximab

Infliximab is an immune-suppressing drug for the treatment of several inflammatory diseases such as Crohn’s, ulcerative colitis, and rheumatoid arthritis [818283].

Infliximab kills monocytes, which may help reduce inflammation in patients with chronic inflammatory diseases [84].

Low Levels of Monocytes (Monocytopenia)

In monocytopenia, the number of monocytes circulating in the blood is decreased to less than 0.2×109/L in adults. Monocytopenia itself does not have symptoms, and patients usually only show symptoms related to its associated diseases, such as fatigue and fever [20, 85].

Conditions Associated with Monocytopenia

  • Aplastic anemia [86]
  • Leukemia (hairy-cell leukemia, chronic lymphocytic leukemia) [87]
  • Chemotherapy [88]
  • MonoMAC syndrome (monocytopenia and Mycobacterium Avium Complex syndrome) [89]
  • Severe burn injuries [90]
  • Rheumatoid arthritis [91]
  • Systemic lupus erythematosus [92]
  • HIV infection [93]
  • Vitamin B12 deficiency [94]
  • Corticosteroid therapy (transient monocytopenia) [95]
  • Administration of INF-alpha and TNF-alpha [96]
  • Radiation therapy [97]

Health Effects Low Levels

1) Lower the Risk of Cardiovascular Disease

Out of all white blood cells, monocyte count has the strongest relationship with overall cardiovascular disease development in people with no symptoms.

Lower levels of monocytes are associated with lower cardiovascular risk [98].

2) Increase Susceptibility to Infections

Low monocyte counts increase susceptibility to infections.

Monocytopenia is associated with MonoMAC syndrome, which is characterized by increased susceptibility to mycobacterial, fungal, and human papillomavirus (HPV) infections [8920].

3) Are Associated with a Risk of Blood Disorders

Monocytopenia is associated with a high risk of development of hematologic disorders such as myelodysplasia, acute myelogenous leukemia, chronic myelomonocytic leukemia, and lymphomas [89].

4) Increase the Risk of Cervical Cancer

Due to monocytopenia, patients with primary immunodeficiency are susceptible to severe, persistent human papillomavirus (HPV) infections that can cause cervical cancer [99].

Ways to Increase Monocyte Levels

1) Acute Strenuous Exercise

During the first few minutes of strenuous exercise, monocytes rapidly increase in the blood, but their numbers quickly decrease after the activity is done [100].

2) Sauna

Sauna increases levels of white blood cells and monocytes, more so in athletes than in untrained subjects. This is because overheating the human body leads to elevated activity of monocytes [101].

3) Cold Exposure

Prolonged cold exposure increases the number of monocytes through the “fight or flight” (sympathetic) nervous system activation [100].

4) Growth Hormone

Growth hormone injections increase white blood cell counts, which also increase monocyte counts [102].

5) Testosterone

Injections of testosterone into mice increased the number of monocytes, granulocytes, and large lymphocytes in the blood [103].

6) Vitamin B12

Vitamin B12 helps increase white blood cell count (including monocytes) in rats with protein deficiencies. However, supplementation with vitamin B12 does not change white blood cell count in rats that ate normal amounts of protein [104].

7) Vitamin C

Recent studies suggest that vitamin C can modify immunity by inhibiting the programmed death of monocytes [105].

8) Calcitriol (Vitamin D)

Calcitriol (vitamin D) can increase the growth of human monocytes [106].

9) Garlic

Garlic increases the total white blood cell count. Rats fed garlic had significantly more monocytes, neutrophils, and lymphocytes than rats not fed with garlic [107].

Factors That Increase Monocytes

1) Leptin

Human leptin increases monocyte growth and cytokine production because leptin is a proinflammatory cytokine [108].

Leptin levels correlate with body weight.

2) Menopause

There is an increase in blood monocyte number during menopause. Moreover, monocyte counts decline following estrogen replacement therapy [109].

3) Chronic Alcohol Drinking

Alcohol consumption causes leaky gut, which allows lipopolysaccharides from gram-negative bacteria in the gut to cause inflammation. Acute alcohol consumption initially mitigates the inflammation from LPS. However, chronic alcohol consumption can lead to a gradual increase of monocytes and inflammatory proteins, contributing to a general body state of inflammation [110].

Prolonged alcohol intake also resulted in an increase in TNF-alpha production by monocytes [77, 111].

Irregular Monocyte Levels?

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