Mitochondrial Dysfunction is Associated With an Immune Paralysis Phenotype in Pediatric Sepsis.
Shock
; 54(3): 285-293, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-31764621
OBJECTIVE: Immune dysregulation is a defining feature of sepsis, but the role for mitochondria in the development of immunoparalysis in pediatric sepsis is not known. We sought to determine if mitochondrial dysfunction measured in peripheral blood mononuclear cells (PBMCs) is associated with immunoparalysis and systemic inflammation in children with sepsis. DESIGN: Prospective observational study. SETTING: Single-academic pediatric intensive care unit (PICU). PATIENTS: One hundred sixty-one children with sepsis/septic shock and 18 noninfected PICU controls. MEASUREMENTS AND MAIN RESULTS: Mitochondrial respiration in PBMCs, markers of immune function, and plasma cytokines were measured on days 1 to 2 (T1), 3 to 5 (T2), and 8 to 14 (T3) after sepsis recognition, and once for controls. Immunoparalysis was defined as whole-blood ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α) ≤200âpg/mL or monocyte human leukocyte antigen-DR ≤30%. Mitochondrial respiration was lower in children with versus without immunoparalysis measured at the same timepoint. Mitochondrial respiration measured early (at T1 and T2) was also lower in those with immunoparalysis at T2 and T3, respectively. Although most patients with immunoparalysis exhibited low mitochondrial respiration, this metabolic finding was not specific to the immunoparalysis phenotype. Plasma cytokines, including IL-8, IL-10, TNF-α, and MCP-1, were highest in the subset of sepsis patients with immune paralysis or low mitochondrial respiration at T1. CONCLUSIONS: Children with sepsis had lower PBMC mitochondrial respiration when immunoparalysis was present compared with those without immunoparalysis. The subsets with immune paralysis and low mitochondrial respiration exhibited the highest levels of systemic inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sepse
/
Inflamação
/
Mitocôndrias
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Humans
/
Male
Idioma:
En
Revista:
Shock
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de publicação:
Estados Unidos