Reduced frequency of CD56dim CD16pos natural killer cells in pediatric systemic inflammatory response syndrome/sepsis patients

Halstead, E. Scott; Carcillo, Joseph A.; Schilling, Bastian; Greiner, Robert; Whiteside, Theresa L.

doi:10.1038/pr.2013.121

Cited by 28 publications

(24 citation statements)

References 22 publications

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“…These alterations appear to be associated with increased mortality in septic humans (57)(58)(59). Additionally, NK cell cytotoxic function is decreased (60).…”

Section: Introductionmentioning

confidence: 99%

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Delano¹,

Ward²

2016

Journal of Clinical Investigation

526

472

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Sepsis affects the immune system by directly altering the lifespan, production, and function of the effector cells responsible for Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after "recovery" from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical "recovery," with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.

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“…These alterations appear to be associated with increased mortality in septic humans (57)(58)(59). Additionally, NK cell cytotoxic function is decreased (60).…”

Section: Introductionmentioning

confidence: 99%

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Delano¹,

Ward²

2016

Journal of Clinical Investigation

526

472

View full text Add to dashboard Cite

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“…The third phenotype, immune paralysis associated MODS, has impaired ability to kill infection which can be related in part to environmental factors that induce lymphoid depletion such as chemotherapy, prolonged use of dexamethasone, and overuse of immune suppressants (63–65). Treatments may include immune suppressant tapering and use of granulocyte-macrophage colony-stimulating factor (GM-CSF) (64–67). …”

Section: State Of the Sciencementioning

confidence: 99%

Pathophysiology of Pediatric Multiple Organ Dysfunction Syndrome

Carcillo

Podd

Aneja

et al. 2017

Pediatric Critical Care Medicine

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Objective To describe the pathophysiology associated with multiple organ dysfunction syndrome (MODS) in children. Data Sources Literature review, research data, and expert opinion Study Selection Not applicable Data Extraction Moderated by an experienced expert from the field, pathophysiological processes associated with MODS in children were described, discussed and debated with a focus on identifying knowledge gaps and research priorities. Data Synthesis Summary of presentations and discussion supported and supplemented by relevant literature. Conclusions Experiment modeling suggests that persistent macrophage activation may be a pathophysiologic basis for MODS. Children with MODS have 1) reduced cytochrome P450 metabolism inversely proportional to inflammation, 2) increased circulating damage associated molecular pattern molecules (DAMPS) from injured tissues, 3) increased circulating pathogen associated molecular pattern molecules (PAMPS) from infection or endogenous microbiome, and 4) cytokine driven epithelial, endothelial, mitochondrial, and immune cell dysfunction. Cytochrome P450s metabolize endogenous compounds and xenobiotics, many of which ameliorate inflammation, whereas DAMPS and PAMPS alone and together amplify the cytokine production leading to the inflammatory MODS response. Genetic and environmental factors can impede inflammation resolution in children with a spectrum of MODS pathobiology phenotypes. Thrombocytopenia associated MODS patients have extensive endothelial activation and thrombotic microangiopathy with associated oligogenic deficiencies in inhibitory complement and ADAMTS13. Sequential MODS patients have sfasL-fas mediated hepatic failure with associated oligogenic deficiencies in perforin and granzyme signaling. Immune paralysis associated MODS patients have impaired ability to resolve infection, and have associated environmental causes of lymphocyte apoptosis. These inflammation phenotypes can lead to macrophage activation syndrome. Resolution of MODS requires elimination of the source of inflammation. Full recovery of organ functions is noted six to eighteen weeks later when epithelial, endothelial, mitochondrial, and immune cell regeneration and reprogramming is completed.

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“…When the sepsis improves with appropriate antibiotics and source control, the NK and CTL cell numbers return to normal and, in turn, their activity turns off macrophage activation/inflammation as the patient recovers. 18 If instead these patients are treated with agents such as etoposide and dexamethasone, the NK and CTL cell numbers are iatrogenically prevented from recovery if not further reduced. In today’s journal, another set of Turkish investigators demonstrate that a multimodal strategy of source removal and anti-inflammatory measures in children without HLH risk factors or genetic mutations is associated with better outcomes than use of the HLH-94 protocol with dexamethasone and chemotherapy in children with risk factors for HLH.…”

mentioning

confidence: 99%