Caspase-1 Activation in Monocyte Subsets Is Associated with Monocyte Distribution Width.

BACKGROUND

Monocyte distribution width (MDW) is a robust early sepsis biomarker. However, the mechanism underlying MDW elevation remains unclear. We evaluated the associations of MDW with monocyte subset proportions (based on CD14/CD16 expression) and caspase-1 activation levels.

METHODS

In total, 98 adults (22 healthy controls, 25 patients with mild infection, 16 non-sepsis intensive care unit patients, and 35 patients with sepsis) were included in this prospective observational study. MDW was measured alongside routine complete blood count (CBC) using a UniCel DxH 800 analyzer (Beckman Coulter). Caspase-1 activity in monocyte subsets was assessed using flow cytometry with Fluorescent Labeled Inhibitor of Caspase- 1 (Immunochemistry Technologies) and quantified as geometric mean fluorescence intensity.

RESULTS

Compared with healthy controls, all patient groups showed reduced classical monocyte frequencies and increased intermediate monocyte frequencies; these variations were moderately associated with elevated MDW. Caspase-1 activity was elevated in all three monocyte subsets across patient groups; patients with sepsis showed significantly higher non-classical monocyte activity than the other two patient cohorts. MDW correlated positively with caspase-1 activity in all subsets, with the strongest correlation in non-classical monocytes (Spearman's ρ=0.762, P <0.001).

CONCLUSIONS

Elevated MDW correlates with altered monocyte subset proportions and enhanced in vivo caspase-1 activation, with a particularly strong association with non-classical monocyte caspase-1 activity. Given that non-classical monocyte caspase-1 activity is markedly increased in patients with sepsis, our results suggest a potential clinically relevant association linking MDW to sepsis-associated monocyte dysfunction, which may inform the interpretation of MDW in clinical practice.