Overview

Monocytosis is characterised by an increased number of monocytes in blood circulation. Monocytes are immune cells with central functions for our body, such as defending our body against microorganisms and participating in tissue healing. Due to their role in the inflammatory process, monocytosis is observed in several inflammatory conditions and can provide prognostic information. Moreover, treatments that target specific monocytes might offer alternative therapies for these conditions in the future. 

What are monocytes?

Monocytes are white blood cells that protect our body against 'invaders'', such as bacteria and fungi. 

Description and function of monocytes 

Monocytes originate in the bone marrow from precursor cells and enter the blood circulation. Upon receiving specific signals associated with a threat, they migrate to tissues and differentiate into macrophages or dendritic cells. Besides macrophages and dendritic cells, they belong to the mononuclear phagocyte system, due to their ability to perform phagocytosis, which describes their ability to 'eat' and destroy particles.¹  Under pathological conditions, monocytes become activated and are recruited to tissues, supporting inflammation, while they also have a role in tissue regeneration and restoration.²

What is monocytosis? 

Definition of monocytosis 

Monocytosis refers to an increased absolute number of more than 1x10⁹ /L monocytes in the blood of adults. It can be a sign of various pathological conditions, ranging from infections to malignancies and inflammatory conditions, therefore it is important to investigate what causes it.   

Importance of monocytes in inflammation

Monocytes play a major role in the inflammatory process, and it is not surprising that monocytosis is observed in several conditions, involving the immune system, including infections, and acute, and chronic inflammatory conditions.³

Mechanisms linking monocytosis and inflammation

Monocytes in tissue infiltration 

Monocytes originate from progenitors in the bone marrow. Different types of monocytes have been described, namely classical and non-classical monocytes. Under steady or inflammatory conditions, they enter the bloodstream and migrate to tissues, where according to signals they receive from their surrounding environment, they can give rise to different types of cells. The specific signals a monocyte encounters in the bone marrow, bloodstream or upon entering a tissue can vary and affect its function and destiny.⁴

Monocyte activation and differentiation 

Role of cytokines and chemokines 

Cytokines are small proteins that are secreted from cells which contribute to the communication of cells, especially during inflammatory processes. Most immune cells display plasticity, which describes their ability to exhibit different functions, according to the signals they receive from their environment. Cytokines include chemokines, interferons, and interleukins, which act as important chemical messages for the cells.

Differentiation into macrophages and dendritic cells 

When macrophages enter a tissue, they differentiate into macrophages or dendritic cells. Differentiation is a maturation process, through which the cells obtain new or additional features and functions. According to the signals they receive from the tissues that they enter, monocytes can give rise to different types of macrophages or dendritic cells.⁴

Pro-inflammatory response

Some macrophage and dendritic cell subsets (total number of cells in a given area) can further enhance the inflammatory process. These pro-inflammatory macrophages are necessary for fighting an infection. However, it also leads to inevitable collateral damage to the tissue. Specifically, macrophages and dendritic cells can produce pro-inflammatory cytokines, supporting the function of other immune cells, such as lymphocytes. Additionally, they can prime naive T cells, activating them to multiply and act against a specific target.³ 

Anti-inflammatory response

Other macrophage subsets contribute to resolving the inflammation. These anti-inflammatory macrophages can engulf dead cells and debris, and secrete important cytokines for immune cell suppression. Moreover, they produce cytokines, central for tissue remodelling and restoration.³ 

Inflammatory conditions associated with monocytosis

Inflammatory conditions associated with monocytosis include rheumatoid arthritis, inflammatory bowel disease, lupus erythematosus, and atherosclerosis. 

Rheumatoid arthritis

Rheumatoid arthritis is an autoimmune disease, meaning that the immune system recognises parts of the body as foreign and attacks them, often causing damage to tissues and organs. Joints are most commonly affected, where persistent synovial inflammation is observed, frequently leading to cartilage and bone destruction.⁵ This leads to joint swelling and pain in patients. An increased absolute number of monocytes is observed in individuals with the condition compared to healthy individuals.⁶

Monocytes have a central role in the pathogenesis of rheumatoid arthritis. They are recruited from the blood to the sites of inflammation, further enhancing it. They secrete cytokines, activating other immune cells, such as T cells and fibroblasts, causing bone destruction. Importantly, they can differentiate into osteoclasts, a cell type specialised in bone remodelling and breakdown.⁵,⁷

Inflammatory bowel disease 

Inflammatory bowel disease is a chronic disorder, characterised by an inflammatory response in the gut. It consists of Crohn's disease, where inflammation is typically observed in the small intestine, and ulcerative colitis which affects the large intestine. Inflammation causes damage in the intestine, resulting in abdominal pain and diarrhoea experienced by patients. 

Monocytosis is observed in the peripheral blood of patients, with some studies suggesting that there is a connection with the activity or severity of the disease.⁸

Circulating monocytes migrate to the intestine and differentiate into macrophages. These cells secrete cytokines that regulate surrounding immune cells, leading to excess inflammation. Moreover, they secrete reactive molecules that degrade the extracellular matrix of the gut. Importantly, macrophages are necessary for the repair of the tissue during phases of disease remission.⁹

Systemic lupus erythematosus (SLE)

Systemic lupus erythematosus, commonly referred to as lupus, is a systemic autoimmune disease. It can affect various body organs, most commonly the skin, joints, and kidneys. Patients might experience a skin rash, joint pain, fever, and fatigue. Monocytosis has been observed in some individuals with the SLE condition and studies show that monocytes of SLE patients present different features compared to monocytes of healthy individuals.¹⁰

In people with active disease, monocytes migrate from the blood to the skin, joints, or glomerulus, differentiating into macrophages that enhance inflammation and tissue damage.¹⁰

Atherosclerosis

Atherosclerosis is a chronic inflammatory condition that can lead to serious health problems, such as stroke and heart attack. Atherosclerotic plaques develop in arteries and break off into the bloodstream, causing thrombosis and blocking blood circulation. A high monocytic number has been linked to increased risk from atherosclerosis.¹¹

High cholesterol levels and low-density lipoproteins also contribute to plaque formation. Specifically, oxidised lipids can be recognised by circulating monocytes or differentiated macrophages, trapping them in the walls of vessels. This leads to the accumulation of lipids in the cells, leading to foam cell formation, and further growth of atherosclerotic plaques.¹¹

Other inflammatory conditions 

Monocytosis has been associated with psoriatic arthritis, an inflammation of joints observed in people with skin psoriasis.¹² Additionally, some patients with sarcoidosis display increased monocyte numbers in their blood.¹³ Monocytes differentiate into pro-inflammatory macrophages in these conditions, further exacerbating tissue damage in the affected organs. 

Why is monocytosis important in inflammatory conditions?

Diagnostic value 

Detection of monocytosis can be a valuable tool for diagnosing or further evaluating a condition. It is important to note, that a high monocyte number is not bound to a specific condition, but rather provides important additional information.¹⁴  For example, it can indicate a probable involvement of joints in an inflammatory disease.¹³  

Prognostic value 

It has been noticed that in some patients, monocyte numbers correlate with disease activity or severity.^6,8 Therefore, it is important to observe these fluctuations and administer treatments, when necessary. During treatment and remission phases these numbers might decrease.⁸ 

Therapeutic implications 

Since monocytes are involved in the inflammatory process of several conditions, blocking them or the cytokines they secrete, holds therapeutic potential. Several cytokines that are secreted from these cells are targeted in the case of rheumatoid arthritis.¹⁵ 

Future directions

Several studies have indicated that the types of circulating monocytes, or the tissue environment that shapes them are implicated in several inflammatory conditions. Further research and understanding of monocytosis can hold both prognostic and therapeutic value. Using small particles, called nanoparticles, that can specifically target and modify the function of monocytes, is evaluated for clinical use and is a promising future direction for those conditions.¹⁶

FAQs

Is monocytosis always linked to a serious inflammatory condition?

The reason behind an increased number of monocytes in circulation is not always a serious condition. Several infections can also lead to abnormal numbers. The clinician will consider other symptoms, additional tests, and the history of an individual before diagnosis.¹⁴

Summary

Inflammatory conditions include disorders marked by abnormal inflammation. Monocytes are immune cells that can either promote or suppress the inflammatory process. As a result, monocytosis is a term describing an abnormally increased monocyte number, and it is found in some cases of inflammatory conditions. These include rheumatoid arthritis, inflammatory bowel, systemic erythematosus, and atherosclerosis among others. Monocytosis can give information about the activity or severity of inflammatory conditions.