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Antioxidant protection against iron in children with meningococcal sepsis
Marino Festa1, Sharon Mumby, Simon Nadel
1Paediatric Intensive Care Unit, Imperial College School of Medicine at St Mary's Hospital, London, UK.
Insights
Children with meningococcal sepsis show impaired antioxidant defenses against iron-induced oxidative stress. These deficiencies in antioxidant protection are linked to the severity of the illness.
Area of Science:
- Pediatric Intensive Care
- Infectious Diseases
- Biochemistry
Background:
- Meningococcal sepsis can lead to severe illness and death.
- Iron metabolism plays a role in oxidative stress during infections.
- Antioxidant systems are crucial for combating reactive oxygen species.
Purpose of the Study:
- To evaluate antioxidant protection against iron-catalyzed reactive oxygen species in pediatric meningococcal sepsis.
- To determine if illness severity correlates with deficiencies in antioxidant systems.
Main Methods:
- A prospective, controlled study was conducted in a pediatric intensive care unit.
- Twenty children with meningococcal septic shock were analyzed, with paired convalescent samples obtained.
- Disease severity was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score.
Main Results:
- Patients with acute meningococcal sepsis exhibited decreased transferrin levels and iron-binding capacity, with increased transferrin iron saturation.
- Iron-binding antioxidant protection was diminished in more severe cases, correlating significantly with disease severity.
- Iron-oxidizing antioxidant protection was also reduced in acute sepsis and correlated with disease severity and plasma ceruloplasmin levels.
Conclusions:
- Children with meningococcal septicemia display altered plasma iron chemistry.
- There is decreased protection against iron-catalyzed oxidative damage in these patients.
- These antioxidant deficiencies are significantly correlated with the severity of meningococcal sepsis.
Objective:
To assess antioxidant protection against iron-catalyzed reactive oxygen species in meningococcal sepsis and to establish whether severity of illness is related to deficiencies in these antioxidant systems.
Design:
Prospective, controlled study.
Setting:
Pediatric intensive care unit of a postgraduate teaching hospital.
Patients:
Twenty children aged 6 months to 15 yrs (median, 5 yrs) with meningococcal septic shock were studied. Paired convalescent samples taken 8-10 wks after discharge were available in nine children.
Interventions:
Routine management for meningococcal sepsis.
Measurements And Main Results:
Patients were classified for disease severity using the Glasgow Meningococcal Septicaemia Prognostic Score. Paired acute and convalescent samples were compared. Transferrin level (1.77 +/- 0.08 g/L) and total iron-binding capacity (46.2 +/- 2.0 microM) were significantly decreased in acute patients compared with paired convalescent samples (2.85 +/- 0.10 g/L and 74.4 +/- 2.5 microM, respectively; p <.0001). The iron saturation of transferrin was significantly increased in acute disease (36.9% +/- 2.5%) compared with convalescence (18.8% +/- 1.5%; p =.0003). Iron-binding antioxidant protection was not significantly different in acute (81.4% +/- 1.7%) and paired convalescent samples (85.6% +/- 2.5%; p =.54). However, patients with more severe meningococcal septicemia (GMSPS, >10; n = 12) had significantly diminished protection (77.5% +/- 2.4%) compared with less severe disease (87.1% +/- 1.6%; p =.0028), and there was a significant correlation between disease severity and iron-binding antioxidant protection (R =.48; p =.00067) in acute disease. Paired ceruloplasmin levels were available in six patients and were decreased in acute disease (0.29 +/- 0.02 g/L) compared with convalescence (0.40 +/- 0.04 g/L), although not statistically significant (p =.076). However, there was a significant correlation between plasma ceruloplasmin and disease severity (Pearson product moment correlation, p =.038) in the acute patients. Iron-oxidizing antioxidant assays were performed in four paired samples and were diminished in acute patients (53.3 +/- 4.4%) compared with convalescence (67.8 +/- 3.2%; p =.015). Acute samples demonstrated a significant relationship between iron-oxidizing antioxidant protection and both disease severity (r =.30; p =.012) and plasma ceruloplasmin levels (r =.48; p =.00067).
Conclusions:
Children with meningococcal septicemia exhibit abnormal plasma iron chemistry and decreased protection against iron-catalyzed oxidative damage. Such deficiencies correlate with disease severity.