Comparative analysis of monocyte distribution width alterations in Escherichia coli sepsis: insights from in vivo and ex vivo models

Objectives: Monocyte distribution width (MDW) is an early sepsis indicator measuring monocyte heterogeneity during massive infection. We compared MDW changes in Escherichia coli sepsis patients with the effects of living E. coli and lipopolysaccharide in an ex vivo sepsis model. We also investigated the dynamics of monocyte morpho-functional and inflammatory responses in the sepsis model. Methods: Whole blood from healthy participants was in vitro stimulated with live E. coli (106-1010 CFU/mL) and LPS (0.1-10 μg/mL). Complete blood counts, including MDW, were evaluated at different time-points using DxH 690T Hematology Analyzer (Beckman Coulter). MDW values were compared with those retrospectively obtained from sepsis patients (n=23). May-Grunwald-Giemsa-stained blood smears were analyzed by digital cell morphology (CellaVision DM software). A panel of 27 inflammatory mediators was quantified in plasma (Bio-Plex 200). Results: MDW values were early and significantly increased in a dose- and time-dependent manner by live E. coli and LPS treatments (p<0.01). MDW values were significantly higher in sepsis patients compared to controls and overlapped those observed in the ex vivo model. IL-1β, TNF-α, IL-8, MIP1-α, MIP-1β, Eotaxin, G-CSF, and PDGF-bb were significantly modulated after treatments. Conclusions: Our findings confirm the clinical utility of MDW in sepsis diagnosis and sustain the reliability of the whole blood assay as ex vivo sepsis model. E. coli and LPS directly promote early monocyte morpho-functional modifications, mirrored by high MDW values and pro-inflammatory mediators. These results improve the knowledge on the biological basis of sepsis, providing novel evidence on the usefulness of MDW in septic conditions.