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Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are increased in the plasma of children with
M J Whalen1, L A Doughty, T M Carlos
1Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh, PA, USA.
Insights
In children with sepsis-induced multiple organ failure (MOF), elevated levels of vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 indicate a proinflammatory state. These molecules predict organ failure and mortality in pediatric sepsis.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Sepsis research
Background:
- Sepsis-induced multiple organ failure (MOF) is a critical condition in children.
- Circulating adhesion molecules play a role in inflammatory processes and endothelial activation.
Purpose of the Study:
- To measure concentrations of endothelial (E)-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 in children with sepsis-induced MOF.
- To investigate the association between these adhesion molecules and clinical outcomes in pediatric sepsis.
Main Methods:
- Prospective study conducted in a university pediatric intensive care unit.
- Measured plasma E-selectin, ICAM-1, and VCAM-1 in 77 children with sepsis and 14 controls.
- Utilized multivariate logistic regression to analyze associations with organ failure and mortality.
Main Results:
- Children with sepsis showed increased E-selectin, ICAM-1, and VCAM-1 compared to controls.
- Elevated VCAM-1 correlated with more severe organ failure (more than three organs).
- ICAM-1 and VCAM-1 independently predicted the number of failed organs, mortality, and sequential MOF.
Conclusions:
- Persistent elevation of VCAM-1 and ICAM-1 in pediatric sepsis with MOF suggests a proinflammatory endothelial phenotype.
- Activated leukocytes may also contribute to increased adhesion molecule levels.
- Further research is needed to elucidate the role of ICAM-1 and VCAM-1 in the pathogenesis of sepsis-induced MOF.
Objectives:
To determine concentrations of circulating adhesion molecules endothelial (E)-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 in children with sepsis-induced multiple organ failure (MOF), and to determine associations among increased concentrations of these circulating adhesion molecules and important outcome measures.
Design:
Prospective study.
Setting:
University pediatric intensive care unit.
Patients:
A total of 77 consecutive children with sepsis and 14 acutely ill children without sepsis.
Interventions:
Plasma E-selectin, ICAM-1, and VCAM-1 concentrations and organ failure index (indicating number of failed organ systems) were determined in 77 children on days 1 and 3 of sepsis, and in 14 control children on pediatric intensive care unit day 1. Multivariate logistic regression analysis was used to determine associations between adhesion molecule concentrations and clinically relevant outcome measures.
Measurements And Results:
Plasma concentrations of E-selectin, ICAM-1, and VCAM-1 were increased in children with sepsis vs. control on day 1 (p < .05). Plasma VCAM-1 (but not ICAM-1 or E-selectin) was increased in children with more than three organ failures vs. children with less than three organ failures (p < .05). Plasma ICAM-1 and VCAM-1 (but not E-selectin) concentrations independently predicted number of organs failed and development of more than three organ failures. Plasma ICAM-1 and VCAM-1 also predicted mortality and development of sequential (pulmonary/hepatic/renal) MOF (p < .05).
Conclusions:
The pronounced and persistent increase in plasma VCAM-1 and ICAM-1 that occurs in children with sepsis and persistent MOF may indicate a phenotypic change in endothelium toward a more proinflammatory state. Alternatively, the source for these adhesion molecules may be activated leukocytes and other cell types. Future studies are required to determine the role of ICAM-1 and VCAM-1 in the pathogenesis of sepsis-induced MOF.