Neutrophil and Monocyte Phagocytosis in Children With Septic Shock

Introduction: Septic shock is an important source of morbidity and mortality in children worldwide. Neutrophil activation and proinflammatory responses are often identified as key factors in sepsis pathophysiology. Sepsis-induced immune suppression may also contribute to morbidity, though little is known about neutrophil suppression in pediatric sepsis. We conducted a prospective observational study to evaluate monocyte and neutrophil phagocytic function in children with septic shock.


Methods: The study was approved by the Institutional Review Board. Children ages 4mo to 18y who were within 48 hrs of septic shock onset were included, excluding children with ANC < 500. Phagocytosis assays, monocyte HLA-DR and neutrophil CD88 expression were quantified by flow cytometry. Data are median (interquartile range). Comparisons between groups analyzed with Mann Whitney or Fishers exact test.


Results: A total of 23 children with septic shock aged 10.3 (2.8,14) years, 52% male were included in the study. PRISM III score 12 (7,15) and VIS 10 (7,20). Ten healthy controls aged 9.4 (4,12) yrs, 50% male were included (p NS vs septic patients). Sepsis patients had a lower proportion of neutrophils expressing CD88 compared to healthy controls (97.6% [94.3,98.1] vs. 99.4% [99.1,99.6]; p < 0.0001). Sepsis patients had lower proportions of neutrophils and monocytes with intact phagocytic function (neutrophils: 76.5% [39,88] vs. 98% [95,99], p < 0.0001; monocytes: 64% [41,83] vs. 99.5% [99.3,99.7], p < 0.0001). Within the septic shock group, significant correlation between monocyte HLADR expression and monocyte or neutrophil phagocytotic function were not observed (r=0.33, p=0.1 and r=0.36, p=0.1, respectively).


Conclusions: This cohort of children with septic shock demonstrated evidence of diminished neutrophil function compared to healthy children. Among sepsis patients, neither monocyte nor neutrophil phagocytosis assays correlated with monocyte HLADR, a commonly used marker of sepsis-induced immune suppression. This suggests that mechanisms and markers of sepsis induced immune suppression may vary in individual patients and that multiple biomarkers may be needed. Additional studies are needed to confirm these findings and to relate measures of neutrophil function to clinical outcomes in septic children.