Neutrophils and Interleukin-18's Dual Roles in Sepsis Pathogenesis Explored in Review

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, leading to organ dysfunction. Current treatments often fall short due to the complex and dynamic nature of the inflammatory response. Neutrophils are critical immune cells that combat pathogens, but their uncontrolled activation can exacerbate tissue damage. Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine, closely linked to inflammasome activation, which significantly influences neutrophil behavior and the overall inflammatory cascade in sepsis, highlighting a critical gap in fully understanding their combined impact.

This article systematically reviewed existing literature on the functions of neutrophils and interleukin-18 in sepsis. The authors synthesized findings regarding neutrophil migration, activation, and their dual role as both pathogen combatants and immune regulators. The review also focused on IL-18's role as a classical inflammasome-associated pro-inflammatory factor and its imperative influence on neutrophil behavior. The aim was to consolidate current understanding to provide a theoretical basis for further in-depth exploration of sepsis pathogenesis and the development of targeted therapeutic strategies.

The review highlighted that neutrophils are not merely effector cells combating microbial infections but also crucial regulators of immune responses, playing a 'double-edged sword' role in sepsis. Their activation and migration are tightly controlled, yet can become dysregulated. Interleukin-18 (IL-18) was identified as a classical inflammasome-associated potent pro-inflammatory factor. A key finding was the imperative role of IL-18 in the migration and activation of neutrophils, suggesting a direct link between this cytokine and neutrophil-mediated pathology. The complex interplay between IL-18 and neutrophil dynamics significantly contributes to the dysregulated inflammatory responses observed in sepsis. This synthesis of roles provides a clearer picture of the intricate mechanisms driving sepsis progression.

Neutrophils exhibit a 'double-edged sword' role in sepsis, acting as both key pathogen combatants and crucial regulators of immune responses, with IL-18 playing an imperative role in their activation and migration.