Hyporesponsiveness of natural killer cells and impaired inflammatory responses in critically ill patients

Kim, Minkyung; Jeong, Hana; Chae, Jey Sook; Kim, Young Sam; Lee, Jae-Gil; Cho, Younsoo; Lee, Jong Ho

doi:10.1186/s12865-017-0231-y

Cited by 13 publications

(16 citation statements)

References 42 publications

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“…This LPS tolerance state is associated with decreased capacity of whole blood and peripheral mononuclear cells to produce proinflammatory cytokines in response to LPS stimulation. Decreased levels of proinflammatory cytokines IL-6 and TNF-α in the serum and in the peripheral mononuclear cells (PBMC) supernatant are found in response to LPS stimulation in critically ill patients in ICU in comparison to healthy individuals [31]. Similar results were seen in our study, the level of TNF-α rose with LPS stimulation to a lesser degree than in children with NE compared to age-matched controls.…”

Section: Discussionsupporting

confidence: 90%

Cytokine dysregulation persists in childhood post Neonatal Encephalopathy

et al. 2020

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Background: Cytokines are possible mediators of neuroinflammation and associated with adverse outcome in neonatal encephalopathy (NE). Our aim was to explore cytokine response in children with Neonatal Encephalopathy (NE) at school age compared to age-matched controls. Method: Follow up at school age, children who had NE and age-matched controls were assessed for their cytokine responses and neurodevelopment outcome. Pro-and anti-inflammatory cytokines in the serum, [Interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, IL-18, Tumor necrosis factor (TNF)-α, TNF β, Interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), erythropoietin (EPO), IL-10 & IL-1RA] were measured at baseline and in response to in vitro stimulation with lipopolysaccharide (LPS: endotoxin). Results: GM-CSF, TNF-β, IL-2 IL-6 and IL-8 were significantly elevated at school age following NE (n = 40) compared to controls (n = 37). A rise in GM-CSF, IL-8, TNF-α, IL-1β, & IL-6 were seen in NE group following LPS stimulation. Relative LPS hypo-responsiveness was also noted in children with severe NE with IL-10, VEGF, EPO and TNF-β. Elevated TNF-β was associated with low gross motor scores on assessment at school age. Conclusion: School-age children post-NE had significantly altered cytokine responses to endotoxin compared to controls. TNF-β was associated with adverse developmental outcomes. This suggests the inflammatory process may persist into childhood and a longer therapeutic window may be available for neuroprotection therapies.

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Section: Discussionsupporting

confidence: 90%

Cytokine dysregulation persists in childhood post Neonatal Encephalopathy

et al. 2020

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Section: Immunologic Consequences Of Critical Illnessmentioning

confidence: 99%

“…Activation of the immune system occurs with stressors such as sepsis, trauma, surgery, burns, ischemia‐reperfusion, and cancer . The immunologic derangements are manifest in both innate and adaptive immunity . This response has been characterized by both an exacerbation of proinflammatory mediators and a compensatory release of anti‐inflammatory substances or hyporesponsiveness .…”

Section: Immunologic Consequences Of Critical Illnessmentioning

confidence: 99%

“…6 The immunologic derangements are manifest in both innate and adaptive immunity. 6,7 This response has been characterized by both an exacerbation of proinflammatory mediators and a compensatory release of anti-inflammatory substances or hyporesponsiveness. [6][7][8] This phenomenon has received greater attention due to scientific advances in clinical genomics as scientists propose that early leukocyte genomic response is consistent with simultaneously increased gene expression in the innate immune response and the compensatory anti-inflammatory response, with simultaneous suppression of genes involved in adaptive immunity.…”

Section: Immunologic Consequences Of Critical Illnessmentioning

confidence: 99%

“…6,7 This response has been characterized by both an exacerbation of proinflammatory mediators and a compensatory release of anti-inflammatory substances or hyporesponsiveness. [6][7][8] This phenomenon has received greater attention due to scientific advances in clinical genomics as scientists propose that early leukocyte genomic response is consistent with simultaneously increased gene expression in the innate immune response and the compensatory anti-inflammatory response, with simultaneous suppression of genes involved in adaptive immunity. 4 The innate immune-system response initiated by circulating monocytes is evident from elevations in proinflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), as well as elevations in anti-inflammatory cytokines such as IL-10 and the IL-1 receptor antagonist.…”

Section: Immunologic Consequences Of Critical Illnessmentioning

confidence: 99%

See 2 more Smart Citations

Immunonutrition in Critical Illness: What Is the Role?

McCarthy

Martindale

2018

Nut in Clin Prac

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Acute illness-associated malnutrition leads to muscle wasting, delayed wound healing, failure to wean from ventilator support, and possibly higher rates of infection and longer hospital stays unless appropriate metabolic support is provided in the form of nutrition therapy. Agreement is still lacking about the value of individual immune-modulating substrates for specific patient populations. However, it has long been agreed that there are 3 primary targets for these substrates: 1) mucosal barrier function, 2) cellular defense function, and 3) local and systemic inflammation. These targets guide the multitude of interventions necessary to stabilize and treat the hypercatabolic intensive care unit patient, including specialized nutrition therapy. The paradigm shift that occurred 30 years ago created a unique role for nutrition as an agent to support host defense mechanisms and prevent infectious complications in the critically ill patient. This overview of immunonutrition will discuss the evidence for its role in critical illness today.

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A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis

et al. 2021

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Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation syndrome characterized by uncontrolled immune cell activation. Timely diagnosis is important, since early treatment can improve survival rates. However, completing all assessments needed to reach ≥5 positive criteria out of the 8 HLH-2004 criteria can be time consuming and may delay timely initiation of treatment. Hence, we applied a data-driven approach to identify a minimal parameter set for early decision-making towards the initiation of HLH-specific treatment. We retrospectively evaluated 165 patients from five Dutch tertiary hospitals with suspected HLH. Sixteen pHLH (median age 0.5 years) and 70 sHLH patients (median age 8.7 years) were identified using the HLH-2004 criteria. Clustering analysis and multi-receiver operator characteristics were used to identify parameters distinctive of HLH. The presence of either increased ferritin, cytopenia in ≥2 lineages, or splenomegaly distinguished HLH from non-HLH cases with a negative predictive value of 100%. A minimal parameter set consisting of 2 major criteria (phagocytosis and splenomegaly) and 3 minor criteria (cytopenia, increased ferritin, and increased triglycerides/low fibrinogen) predicted HLH with 95% (88–99) sensitivity and 94% (86–98) specificity. This finding was replicated in an independent retrospective validation cohort of 109 US patients (n = 109). By dividing a subset of the HLH-2004 criteria into major and minor criteria, this strategy uses the evaluation of less than 5 criteria to quickly identify patients with HLH. When confirmed in a prospective setting, this approach could be of value for timely diagnosis and treatment of HLH.

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Hyporesponsiveness of natural killer cells and impaired inflammatory responses in critically ill patients

Cited by 13 publications

References 42 publications

Cytokine dysregulation persists in childhood post Neonatal Encephalopathy

Cytokine dysregulation persists in childhood post Neonatal Encephalopathy

Immunonutrition in Critical Illness: What Is the Role?

A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis

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