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Elevated interleukin-1 receptor antagonist levels in pediatric sepsis syndrome
L M Samson1, U D Allen, W D Creery
1Department of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario, Canada.
Insights
Children with sepsis syndrome have high levels of interleukin-1 receptor antagonist (IL-Ira) upon hospital admission. These elevated IL-Ira levels may block IL-1 receptors, questioning the benefit of additional IL-Ira therapy in sepsis patients.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Infectious diseases
Background:
- Sepsis syndrome is a life-threatening condition in children.
- Cytokines play a crucial role in the inflammatory response during sepsis.
- Interleukin-1 receptor antagonist (IL-Ira) is an endogenous inhibitor of interleukin-1 (IL-1).
Purpose of the Study:
- To quantify plasma levels of key inflammatory cytokines, including IL-1 beta, IL-Ira, and tumor necrosis factor alpha, in pediatric sepsis patients.
- To compare cytokine levels in children with sepsis to age-matched healthy controls.
Main Methods:
- Prospective, observational study involving 14 pediatric patients with sepsis syndrome.
- Cytokine levels measured using enzyme-linked immunosorbent assay (ELISA) at multiple time points (baseline, 12, 24, 48 hours).
- Comparison of cytokine levels between sepsis patients and 21 age-matched control subjects.
Main Results:
- Septic children exhibited significantly elevated IL-Ira plasma levels compared to controls across all measured time points (p < 0.001 at baseline and 12 hours).
- IL-Ira levels were substantially higher (over 1000-fold) than IL-1 beta levels in most septic patients.
- Bacterial and viral sepsis were identified in 5 and 3 patients, respectively.
Conclusions:
- Circulating IL-Ira levels in pediatric sepsis patients at admission are sufficiently high to potentially block IL-1 receptors.
- The therapeutic benefit of administering exogenous IL-Ira to these patients is questionable.
- Further research is needed to identify specific sepsis patient subgroups who might benefit from exogenous IL-Ira therapy.
Objective:
To measure plasma levels of interleukin-1 beta, interleukin-1 receptor antagonist (IL-Ira), and tumor necrosis factor alpha in children with sepsis syndrome.
Study Design:
A prospective, observational study of 14 patients aged 5 months to 13 years with sepsis syndrome admitted to a pediatric intensive care unit. Cytokine levels were measured by enzyme-linked immunosorbent assay at baseline and at a 12, 24, and 48 hours and compared with the levels of 21 age-matched control subjects.
Results:
The mean pediatric risk of mortality score was 16.1. Bacterial and viral sepsis was confirmed in five and three patients, respectively. Compared with the levels in the control subjects (mean level of IL-Ira: 654 pg/ml), the IL-Ira levels were elevated in the septic patients, with mean values of 17855 (p < 0.001), 12771 (p < 0.001), 9182 (p < 0.01), and 2296 pg/ml (p = not significant) at baseline and at 12, 24, and 48 hours, respectively. The IL-Ira level was greater than 1000-fold higher than the IL-1 beta level at all time points in 13 of 14 septic patients.
Conclusions:
At the time of hospital admission, circulating IL-Ira levels in a cohort of children with sepsis syndrome were at concentrations known to block IL-1 receptors. Thus additional benefit from exogenous IL-Ira therapy would be questionable. Further studies are indicated to determine whether there is a population of patients with sepsis who could benefit from administration of exogenous IL-Ira.