What is the role of neutrophils (white blood cells) in the body?

The Role of Neutrophils in the Body

Neutrophils are critical immune cells that serve as the first line of defense against infections, particularly bacterial and fungal pathogens, through their phagocytic properties and ability to produce reactive oxygen species to destroy foreign entities.

Primary Functions of Neutrophils

• Neutrophils are the most abundant granulocytes in the body and generally the first and most lethal effector cells recruited to inflammation sites 1
• They play a crucial role in the acute inflammatory response and host defense against bacterial infections through phagocytosis and oxidative burst, which leads to rapid production of oxygen radicals 1, 2
• Neutrophils are essential for providing host defense against infection, with the risk of infection increasing significantly when neutrophil counts decrease below normal levels 1
• They are recruited to sites of infection or injury when protective barriers such as skin or mucosa have been compromised 1

Neutrophils in Infection Control

• When neutrophil counts decrease to less than 500/mcL (neutropenia), susceptibility to infection increases significantly, with the frequency and severity of infection inversely proportional to the neutrophil count 1
• The risk of severe infection and bloodstream infection is greatest when the neutrophil count is less than 100/mcL 1
• In neutropenic patients, common infection sites include the alimentary tract (mouth, pharynx, esophagus, bowel), sinuses, lungs, and skin 1
• Fever is often the only sign of infection in neutropenic patients, as the signs and symptoms of inflammation may be minimal or absent in severely neutropenic patients 1

Advanced Neutrophil Functions

• Beyond their traditional role in pathogen clearance, neutrophils also contribute to adaptive immunity by aiding the development of specific adaptive immune responses 3
• Neutrophils secrete cytokines, chemokines, and antimicrobial components that contribute to pathogen clearance 4
• They can form Neutrophil Extracellular Traps (NETs) to trap and inactivate pathogens, a mechanism extensively studied during bacterial infections but also relevant in antiviral defense 4
• Neutrophils exhibit functional plasticity and can be categorized into different subsets based on their activity profiles, such as N1 (immunostimulating) and N2 (immunosuppressive) in cancer contexts 5

Neutrophils in Disease States

• In cancer patients, neutrophil function can be compromised by chemotherapy, leading to increased risk of infection 1
• Neutrophils play dual roles in tumor development and progression, with different subpopulations showing either pro-tumor or anti-tumor activity 5
• In asthma, particularly refractory asthma, neutrophils may contribute to a different inflammatory process than in milder forms of asthma 1
• Neutrophils can produce substances such as matrix metalloproteinases and oxygen radicals that could alter the structure and function of airways in severe asthma 1
• In some clinical contexts, neutrophil function can be modulated by medications, including volatile anesthetics which can impair neutrophil adhesion and migration 1

Clinical Implications

• Monitoring neutrophil counts is essential in patients receiving chemotherapy, as profound, prolonged neutropenia (neutrophil count <500/mcL for 10 days) is a major risk factor for infection 1
• Filgrastim (G-CSF) can be used to stimulate neutrophil production within the bone marrow and affects neutrophil progenitor proliferation, differentiation, and selected end-cell functions 6
• G-CSF regulates neutrophil production and enhances their functional capabilities, including phagocytic ability, priming of cellular metabolism for respiratory burst, and antibody-dependent killing 6
• Prevention and appropriate management of febrile neutropenia is crucial, as the rate of major complications in this context is approximately 25-30% with mortality up to 11% 1

Caveats and Considerations

• While neutrophils are essential for defense against pathogens, excessive or dysregulated neutrophil activity can contribute to tissue damage 3
• Neutrophils are poorly responsive to steroids, and steroids may actually prolong neutrophil survival by decreasing apoptosis 1
• The traditional view of neutrophils as simple, short-lived cells has evolved; they are now recognized as complex cells capable of a significant array of specialized functions 3, 7
• In certain disease contexts, neutrophil subsets with distinct functional profiles may emerge, requiring careful consideration in therapeutic approaches 5