What is the relationship between infused neutrophils and deterioration of infection?

From the Guidelines

Infused neutrophils can potentially worsen infection in certain circumstances, particularly if they exacerbate the inflammatory response without effectively controlling the pathogen, as noted in the context of febrile neutropenia management 1. When considering the relationship between infused neutrophils and the deterioration of infection, it's crucial to understand the role of neutrophils in host defense against infection, especially bacterial and fungal infections 1. The risk of infection increases with the depth and duration of neutropenia, and the management of febrile neutropenia is critical to prevent major complications and mortality 1.

Key Considerations

• The timing of neutrophil administration is critical, with early intervention generally yielding better outcomes than administration during advanced infection stages 1.
• Close monitoring for signs of clinical deterioration is essential for patients receiving granulocyte transfusions, including vital sign changes, worsening respiratory status, or organ dysfunction.
• Prophylactic corticosteroids may be considered to modulate excessive inflammatory responses during neutrophil infusions, although this should be decided on a case-by-case basis considering the risk-benefit ratio, especially in patients with overwhelming infections.

Management and Prevention

• For patients with persistent fever despite neutrophil recovery, assessment by an infectious disease physician or clinical microbiologist and consideration of antifungal therapy are recommended 1.
• The decision to discontinue antibacterials should be based on the neutrophil count, symptoms, and blood culture results, following guidelines such as those provided by ESMO 1 and ASCO/IDSA 1.

Outcome Prioritization

• Morbidity, mortality, and quality of life are the primary outcomes to consider when deciding on the infusion of neutrophils, weighing the potential benefits of pathogen clearance against the risks of exacerbating the inflammatory response and causing tissue damage 1.

From the Research

Relationship Between Infused Neutrophils and Deterioration of Infection

• Infused neutrophils play a critical role in the defense against bacterial and fungal infections, but they can also contribute to tissue injury associated with autoimmune and inflammatory diseases 2.
• The inflammatory activity of neutrophils must be regulated with precision and timing to prevent tissue damage, and this regulation is achieved through a complex network of mechanisms that control neutrophil survival 2.
• Neutrophils can cause unwanted host tissue damage if their function is dysregulated, leading to pathological and chronic inflammatory conditions 3.
• In physiological inflammation, neutrophils are thought to leave the tissues or undergo programmed cell death, especially apoptosis, once the initial insult has been efficiently dealt with 3.
• Infused neutrophils can display an impressive array of antimicrobial functions, including degranulation, production of reactive oxygen species, phagocytosis, and formation of neutrophil extracellular traps (NET) 4.
• However, some bacterial pathogens have the capacity to circumvent destruction by neutrophils, often involving multiple attributes or characteristics, including the production of virulence molecules that can alter or inhibit neutrophil recruitment, phagocytosis, bactericidal activity, and/or apoptosis 5.

Mechanisms of Neutrophil-Mediated Tissue Damage

• Neutrophils can generate reactive oxygen species and degranulate to release abundant cytotoxic products, making them efficient at killing invading microorganisms, but also potentially causing tissue damage if dysregulated 3.
• The lifespan of neutrophils can be dramatically modulated by a large variety of agents, such as cytokines, pathogens, danger-associated molecular patterns, and pharmacological manipulation, which can impact their ability to cause tissue damage 2.
• Neutrophil heterogeneity, with clear different functional phenotypes, has been described, particularly in cancer and inflammation, which can influence their role in tissue damage and infection 4.

Role of Neutrophils in Infection and Inflammation

• Neutrophils are the first line of innate immune defense against infectious diseases, and they play a crucial role in regulating the immune response in various infections or inflammatory disorders 6.
• Activated neutrophils can provide signals for the activation and maturation of macrophages and dendritic cells, and they are involved in the regulation of T-cell immune response against various pathogens and tumor antigens 6.
• Neutrophils can release various antimicrobial molecules and neutrophil extracellular traps (NETs) to contain infection and inflammation, highlighting their importance in the regulation of both innate and adaptive immunity 6.