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

Objectives: Extracellular histone levels are associated with the severity of many human pathologies, including sepsis and COVID-19. This study aimed to investigate the role of extracellular histones on monocyte distribution width (MDW), and their effect on the release of cytokines by blood cells. Methods: Peripheral venous blood was collected from healthy subjects and treated with different doses of a histone mixture (range 0–200 μg/mL) to analyze MDW modifications up-to 3 h and digital microscopy of blood smears. Plasma obtained after 3 h of histone treatment were assayed to evaluate a panel of 24 inflammatory cytokines. Results: MDW values significantly increased in a time- and dose-dependent manner. These findings are associated with the histone-induced modifications of cell volume, cytoplasmic granularity, vacuolization, and nuclear structure of monocytes, promoting their heterogeneity without affecting their count. After 3 h of treatment almost all cytokines significantly increased in a dose-dependent manner. The most relevant response was shown by the significantly increased G-CSF levels, and by the increase of IL-1β, IL-6, MIP-1β, and IL-8 at the histone doses of 50, 100, and 200 µg/mL. VEGF, IP-10, GM-CSF, TNF-α, Eotaxin, and IL-2 were also up-regulated, and a lower but significant increase was observed for IL-15, IL-5, IL-17, bFGF, IL-10, IFN-γ, MCP-1, and IL-9. Conclusions: Circulating histones critically induce functional alterations of monocytes mirrored by MDW, monocyte anisocytosis, and hyperinflammation/cytokine storm in sepsis and COVID-19. MDW and circulating histones may be useful tools to predict higher risks of worst outcomes.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Monocyte distribution width alterations and cytokine storm are modulated by circulating histones ; volume:61 ; number:8 ; year:2023 ; pages:1525-1535 ; extent:11
Clinical chemistry and laboratory medicine ; 61, Heft 8 (2023), 1525-1535 (gesamt 11)

Urheber
Ligi, Daniela
Lo Sasso, Bruna
Della Franca, Chiara
Giglio, Rosaria Vincenza
Agnello, Luisa
Ciaccio, Marcello
Mannello, Ferdinando

DOI
10.1515/cclm-2023-0093
URN
urn:nbn:de:101:1-2023070114083479394704
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
14.08.2025, 10:55 MESZ

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Beteiligte

  • Ligi, Daniela
  • Lo Sasso, Bruna
  • Della Franca, Chiara
  • Giglio, Rosaria Vincenza
  • Agnello, Luisa
  • Ciaccio, Marcello
  • Mannello, Ferdinando

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