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Plasma concentrations of defensins and lactoferrin in children with severe sepsis
Neal J Thomas1, Joseph A Carcillo, Lesley A Doughty
1Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA.
Insights
In nonneutropenic children with severe sepsis, plasma concentrations of defensins and lactoferrin were elevated. These antimicrobial peptides may play a role in host defense, with lactoferrin linked to organ failure.
Area of Science:
- Pediatric critical care medicine
- Infectious diseases
- Immunology
Background:
- Severe sepsis in children involves complex immune responses.
- Leukocyte-derived antimicrobial peptides like defensins and lactoferrin are crucial in host defense.
- The role of these peptides in nonneutropenic sepsis is not fully understood.
Purpose of the Study:
- To investigate the systemic release of defensins and lactoferrin in nonneutropenic children with severe sepsis.
- To compare peptide levels in nonneutropenic sepsis, neutropenic sepsis, and critically ill controls.
- To explore the correlation between peptide levels, neutrophil count, organ failure, and outcomes.
Main Methods:
- Prospective cross-sectional and longitudinal study in a pediatric intensive care unit.
- Enrollment of 92 children with sepsis and 14 critically ill controls.
- Measurement of plasma defensin and lactoferrin concentrations on Days 1 and 3 of sepsis.
Main Results:
- Nonneutropenic sepsis patients showed significantly higher plasma defensin and lactoferrin levels compared to controls and neutropenic sepsis patients.
- Neutropenic sepsis patients had similar defensin levels but lower lactoferrin levels than controls.
- Plasma defensin and lactoferrin concentrations correlated with white blood cell and neutrophil counts.
- Increased plasma lactoferrin, but not defensin, was associated with organ failure.
Conclusions:
- Elevated circulating defensins and lactoferrin in severe pediatric sepsis are partly dependent on neutrophil count.
- These antimicrobial peptides may contribute to host defense mechanisms in pediatric sepsis.
- Lactoferrin levels may serve as a potential biomarker for organ failure development in this population.
Background:
We hypothesized that systemic release of endogenous leukocyte-derived polypeptide antimicrobial defensins (polymorphonuclear leukocyte-specific) and lactoferrin (polymorphonuclear leukocyte and epithelial cell derived) occurs in nonneutropenic children with severe sepsis.
Methods:
We performed a prospective cross-sectional and longitudinal study in a university children's hospital pediatric intensive care unit. Ninety-two consecutive children meeting criteria for sepsis and 14 critically ill children without sepsis (controls) were enrolled, and plasma defensins and lactoferrin concentrations were measured on Days 1 and 3 of sepsis.
Results:
Nonneutropenic sepsis patients (n = 71) had increased defensins and lactoferrin plasma concentrations compared with critically ill control patients [defensins, 450 ng/ml vs. 150 ng/ml; lactoferrin, 332 ng/ml vs. 176 ng/ml (median values); P < 0.05] and neutropenic sepsis patients [n = 21; defensins, 450 ng/ml vs. 50 ng/ml; lactoferrin, 332 ng/ml vs. 20 ng/ml (median values); P < 0.05]. Neutropenic sepsis patients had similar plasma defensin concentrations and a decrease in plasma lactoferrin concentrations compared with control patients (P < 0.05). Defensins and lactoferrin plasma concentrations correlated to total white blood cell and absolute neutrophil count (P < 0.05). There was no association between plasma defensin concentration and organ failure or outcome; however, increased plasma lactoferrin concentrations were observed with the development of organ failure (P < 0.05).
Conclusion:
These data suggest that increased circulating defensins and lactoferrin release are dependent in part on neutrophil count and might play a role in host defense in children with severe sepsis.