Critical Illness–Induced Immune Suppression: Current State of the Science

Greathouse, Kristin; Hall, Mark W.

doi:10.4037/ajcc2016432

Cited by 22 publications

(16 citation statements)

References 72 publications

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“…Infections were most likely the result of other factors, such as inadequate source control, nosocomial origin, and/or critical illness-induced immune suppression. 22 This study is limited by its single-center retrospective design and by evaluation of nutrition status at a single point in time. The variables chosen were reflective of nutrition status and physiological support on d5, which were hypothesized to have associations with our primary or secondary outcomes.…”

Section: Discussionmentioning

confidence: 99%

Impact of Early Initiation of Enteral Nutrition on Survival During Pediatric Extracorporeal Membrane Oxygenation

Greathouse

Sakellaris

Tumin

et al. 2017

J Parenter Enteral Nutr

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Introduction: Pediatric data related to safety, tolerance, and outcomes of enteral nutrition (EN) for patients requiring extracorporeal membrane oxygenation (ECMO) are lacking. The objectives of this study were to evaluate early nutrition status and timing of EN initiation on survival during pediatric ECMO.Methods: A single center institutional review board–approved retrospective chart review was performed on all pediatric patients requiring ECMO from October 2008 through December 2013. Demographics, ECMO variables, laboratory values, vasoactive inotropic score (VIS), and nutrition data on day 5 (d5) were collected. Patients receiving parenteral nutrition (PN) were compared with those receiving any EN on d5. Analyses were conducted to identify factors influencing survival to completion of ECMO and to discharge.Results: Forty‐nine patients aged 53 ± 76 months met inclusion criteria. Kaplan‐Meier curves demonstrated greater survival to discharge in patients receiving any EN, compared with only receiving PN (P = .031). EN on d5 of ECMO support (P = .040) and a higher percentage of daily energy intake achieved (P = .013) were protective, whereas a higher VIS was associated with increased mortality (P = .010). Multivariable analysis demonstrated EN was no longer associated with survival to discharge (P = .139), whereas energy intake (P = .021) and VIS (P = .013) remained significant.Conclusions: Pediatric patients who received nutrition that was closer to goal energy intake, as well as those who received any EN early during ECMO, had improved survival to hospital discharge.

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Section: Discussionmentioning

confidence: 99%

Impact of Early Initiation of Enteral Nutrition on Survival During Pediatric Extracorporeal Membrane Oxygenation

Greathouse

Sakellaris

Tumin

et al. 2017

J Parenter Enteral Nutr

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“…Meanwhile, new insights uncovered that also anti-inflammatory adaptations are engendered and this even at the very early start of critical illness. Indeed, there is also an increase in circulating anti-inflammatory cytokines and the adaptive immune system is affected, as reflected by a reduced human leucocyte antigen DR expression, increased lymphocyte apoptosis and a reduced capacity of lymphocytes to produce cytokines (13). These alterations persist after the acute phase, and are more apparent in this prolonged phase of critical illness when this "immunoparalysis" translates into an increased susceptibility to opportunistic infections such as opportunistic bacterial infections, invasive fungal infections and reactivation of viruses.…”

Section: Critical Illness Induced Immunosuppressionmentioning

confidence: 99%

Cytomegalovirus: A Troll in the ICU? Overview of the Literature and Perspectives for the Future

Schildermans

Vlieger

2020

Front. Med.

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Cytomegalovirus (CMV) is one of the most pathogenic viruses in human. After a primary infection, CMV resides in the host for life as a latent infection. When immunity is reduced, CMV can escape the suppressive effects of the immune system and lead to viremia and antigenemia. This reactivation, first seen in transplant patients, has also been documented in non-immunocompromised CMV-seropositive critically ill patients and is associated with higher morbidity and mortality. In the latter, it is not clear whether CMV reactivation is an innocent bystander or the cause of this observed worse outcome. Two studies showed no difference in the outcome of CMV-seropositive and seronegative patients. In addition, proof-of-concept studies investigating prophylactic antiviral treatment to prevent CMV reactivation during critical illness, failed to show a beneficial effect on interleukin levels or clinical outcome. Further research is necessary to resolve the question whether CMV replication impairs the prognosis in non-immunocompromised critically ill patients. We here give a concise overview on the available data and propose strategies to further unravel this question. First, post-mortem investigation may be useful to evaluate the effect of viral replication on organ inflammation and function. Second, further research should focus on the question whether the level of viremia needs to exceed a threshold to be associated with worse outcome. Third, clinical and biochemical assessments may help to identify patients at high risk for reactivation. Fourth, preemptive treatment based upon early detection of the virus is currently under investigation. Finally, immune-stimulating biologicals may be beneficial in high-risk groups.

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“…Hyperinflammation may often coexist with a compensatory anti-inflammatory response syndrome (CARS) in sepsis and critical illness, which induces quantitative and qualitative defects in the innate and adaptive immune system [6,7]. When severe and persistent, CARS is referred to as "immunoparalysis", and has been associated with impaired anti-microbial defense, risk of superinfections and increased mortality [8,9]. The immunophenotype of CARS includes increased production of anti-inflammatory cytokines such as IL-10, inefficient antigen presentation, lymphocyte apoptosis and upregulation of inhibitory molecules such as programmed cell death protein (PD)-1 [6].…”

Section: Introductionmentioning

confidence: 99%

The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19)

Henry

Benoit

Vikse

et al. 2020

Clinical Chemistry and Laboratory Medicine (CCLM)

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ObjectivesSevere coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes.MethodsAdult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit.ResultsA total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8.ConclusionsThe hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.

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Critical Illness–Induced Immune Suppression: Current State of the Science

Cited by 22 publications

References 72 publications

Impact of Early Initiation of Enteral Nutrition on Survival During Pediatric Extracorporeal Membrane Oxygenation

Impact of Early Initiation of Enteral Nutrition on Survival During Pediatric Extracorporeal Membrane Oxygenation

Cytomegalovirus: A Troll in the ICU? Overview of the Literature and Perspectives for the Future

The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19)

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