Role of Damage-Associated Molecular Patterns and Uncontrolled Inflammation in Pediatric Sepsis-Induced Multiple Organ Dysfunction Syndrome

Alicia M. Alcamo; Diana Pang; Dalia A. Bashir; Joseph A. Carcillo; Trung C. Nguyen; Rajesh K. Aneja

doi:10.1055/s-0038-1675639

Journal of Pediatric Intensive Care, Table of Contents

J Pediatr Intensive Care 2019; 08(01): 025-031
DOI: 10.1055/s-0038-1675639

Review Article

Georg Thieme Verlag KG Stuttgart · New York

Role of Damage-Associated Molecular Patterns and Uncontrolled Inflammation in Pediatric Sepsis-Induced Multiple Organ Dysfunction Syndrome

Alicia M. Alcamo

¹Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

²Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

,

Diana Pang

³Department of Critical Care Medicine, Children's Hospital of the King's Daughters, Norfolk, Virginia, United States

,

Dalia A. Bashir

⁴Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas, United States

⁵Michael E. DeBakey Veteran Affairs Medical Center, Center for Translational Research on Inflammatory Diseases, Houston, Texas, United States

,

Joseph A. Carcillo

¹Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

²Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

,

Trung C. Nguyen

⁴Section of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas, United States

⁵Michael E. DeBakey Veteran Affairs Medical Center, Center for Translational Research on Inflammatory Diseases, Houston, Texas, United States

,

Rajesh K. Aneja

¹Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

²Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

› Author Affiliations

Abstract

The incidence of multiple organ dysfunction syndrome (MODS) in sepsis varies from 17 to 73% and furthermore, increases the risk of death by 60% when controlled for the number of dysfunctional organs. Several MODS phenotypes exist, each unique in presentation and pathophysiology. Common to the phenotypes is the stimulation of the immune response by pathogen-associated molecular patterns (PAMPs), or danger-associated molecular patterns (DAMPs) causing an unremitting inflammation. Two of the MODS phenotypes are discussed in detail, thrombocytopenia-associated multiple organ failure (TAMOF) and the hyperinflammatory phenotype–macrophage activating syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH). In the end, we will briefly review the role of mitochondrial dysfunction as a significant contributor to the pathogenesis of MODS.

Keywords

pediatric severe sepsis - multiple organ dysfunction syndrome - pathogen-associated molecular patterns - danger-associated molecular patterns - macrophage activation syndrome - hemophagocytic lymphohistiocytosis

Full Text

References

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