Monocyte distribution width alterations and cytokine storm are modulated by circulating histones

Area of Science:

• Immunology
• Hematology
• Pathophysiology

Background:

• Extracellular histones are implicated in severe pathologies like sepsis and COVID-19.
• Understanding histone effects on immune cells is crucial for disease management.

Purpose of the Study:

• Investigate extracellular histone impact on monocyte distribution width (MDW).
• Assess histone-induced cytokine release from blood cells.

Main Methods:

• Human blood samples treated with varying histone concentrations (0-200 μg/mL).
• Monocyte distribution width (MDW) and digital microscopy analyzed.
• Plasma cytokine profiles (24 markers) assessed after 3-hour incubation.

Main Results:

• MDW increased significantly with histone dose and time, linked to monocyte morphological changes.
• Widespread dose-dependent cytokine elevation observed, notably G-CSF, IL-1β, IL-6, MIP-1β, and IL-8.
• Other cytokines including VEGF, TNF-α, and IL-2 also showed significant upregulation.

Conclusions:

• Circulating histones induce monocyte alterations (MDW, anisocytosis) and hyperinflammation.
• MDW and histone levels may serve as biomarkers for predicting adverse outcomes in sepsis and COVID-19.