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Published on: June 24, 2019
Circulating erythropoietin and interleukin-6 concentrations increase in critically ill children with sepsis and
1Department of Critical Care, Children's National Medical Center, Washington, DC, USA.
Insights
Plasma erythropoietin and interleukin-6 (IL-6) are elevated in critically ill children with sepsis or septic shock. These factors may stimulate erythropoietin production, suggesting a role for IL-6 in sepsis-related anemia.
Area of Science:
- Pediatric critical care medicine
- Hematology
- Immunology
Background:
- Sepsis and septic shock can lead to anemia in critically ill children.
- Erythropoietin (EPO) is a hormone that regulates red blood cell production.
- Interleukin-6 (IL-6) is a pro-inflammatory cytokine implicated in various disease states.
Purpose of the Study:
- To investigate the relationship between plasma erythropoietin and IL-6 in critically ill children with sepsis or septic shock.
- To examine the effect of patient plasma on erythropoietin production in vitro.
Main Methods:
- Prospective, controlled clinical and laboratory study.
- Measurement of plasma erythropoietin and IL-6 concentrations in children with sepsis/septic shock and controls.
- In vitro study using Hep 3B cells incubated with patient plasma under hypoxic conditions.
Main Results:
- Children with sepsis or septic shock had significantly higher plasma erythropoietin and IL-6 levels compared to controls.
- Plasma from septic/septic shock patients stimulated erythropoietin production in Hep 3B cells.
- A weak correlation was observed between IL-6 levels and stimulated erythropoietin production.
Conclusions:
- Elevated plasma erythropoietin and IL-6 are present in critically ill children with sepsis or septic shock.
- Plasma factors, potentially including IL-6, may stimulate erythropoietin production in sepsis.
- These findings suggest a role for IL-6 in regulating erythropoietin production in pediatric sepsis.
Objectives:
To investigate a possible relationship between plasma erythropoietin and interleukin-6 (IL-6) in critically ill children with sepsis or septic shock. To examine the modulatory effects of plasma from these patients on erythropoietin production in vitro, employing a cell culture system that uses the erythropoietin-producing Hep 3B cell line.
Design:
A prospective, controlled clinical and laboratory study.
Setting:
A pediatric intensive care unit and research laboratory facility at a children's hospital.
Patients:
Children admitted to the pediatric intensive care unit with the diagnosis of sepsis or septic shock (n = 16), and control patients without infection or anemia (n = 16) were admitted to the study.
Interventions:
None.
Measurements And Main Results:
Blood samples were obtained from 16 children with sepsis or septic shock, and 16 age-matched controls. Plasma erythropoletin and IL-6 concentrations were measured using an enzyme-linked immunoassay. Plasma erythropoietin concentrations were significantly higher in children with sepsis or septic shock (120 +/- 26 mlU/mL) than in controls (10 +/- 2 mlU/mL) (p < .001). Plasma IL-6 concentrations were greater in children diagnosed with sepsis or septic shock (12,405 +/- 6662 pg/mL) than in control patients (7 +/- 1 pg/mL) (p < .001), and higher in septic shock patients (27,469 +/- 13,647 pg/mL) than sepsis patients (688 +/- 258 pg/mL) (p = .03). Hep 3B cells were incubated under hypoxic conditions in media containing plasma from control patients, or patients diagnosed with sepsis or septic shock. Media concentrations of erythropoietin were measured using an enzymelinked immunoassay. Hep 3B cells incubated with plasma from patients diagnosed with sepsis or septic shock produced more erythropoietin (216 +/- 23 mlU/mL) than Hep 3B cells incubated under the same conditions in media containing plasma from control patients (152 +/- 11 mlU/mL) (p = .04). Hypoxic Hep 3B cell erythropoietin production in media incubated with plasma from patients diagnosed with sepsis or septic shock correlated significantly (although weakly) with plasma IL-6 values from these same patients (p = .03, r2 = .28).
Conclusions:
Plasma erythropoietin and IL-6 values are increased in critically ill children with sepsis or septic shock in comparison with controls. The data indicate that one or more plasma factors are responsible for stimulation of hypoxia-induced erythropoietin production in the Hep 3B cell line and suggest a possible role for IL-6 in the regulation of erythropoletin production in critically ill children with sepsis or septic shock.
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