Predictive Value of Monocyte Histocompatibility Leukocyte Antigen-DR Expression and Plasma Interleukin-4 and -10 Levels in Critically Ill Patients With Sepsis

Hynninen, Marja; Pettilä, Ville; Takkunen, O.; Orko, R.; Jansson, Sten‐Erik; Kuusela, Pentti; Renkonen, Risto; Valtonen, Matti

doi:10.1097/01.shk.0000068322.08268.b4

Cited by 96 publications

(66 citation statements)

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“…Some authors found that low monocyte HLA-DR expression is a useful indicator of sepsis and its outcome [23] , but others support our results and found no association between HLA-DR expression and mortality [15,21] .…”

Section: Discussionsupporting

confidence: 81%

“…Current knowledge concerning the role of OS and HLA-DR expression in sepsis remains unresolved. Although some studies found a correlation between OS and outcome [8,21] , these results are contested by others. Perianayagam et al [22] evaluated a cohort of 200 patients with AKI and found that the incidence of sepsis was not significantly different according to the various levels of NADPH oxidase, another OS marker.…”

Section: Discussionmentioning

confidence: 40%

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Oxidative Stress and ‘Monocyte Reprogramming’ in Septic Patients with Acute Kidney Injury Requiring CRRT

Silva¹,

Cal²,

Cruz³

et al. 2008

Blood Purif

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Oxidative stress (OS) and monocyte HLA-DR expression are known to be predictive of mortality in sepsis; nevertheless, limited information exists regarding sepsis with acute kidney injury (AKI). The aim of the study was to correlate these markers with outcome in septic patients with AKI requiring continuous renal replacement therapy (CRRT). Advanced oxidation protein products (AOPP) were measured in 32 patients on days 1, 3, 7, 14, 21, and 28. In 14 we assessed the percentage of monocytes expressing HLA-DR (%DR+) and the HLA-DR mean fluorescence intensity (MFI). 20 healthy volunteers, 17 septic patients without AKI and 20 septic AKI patients not treated by CRRT were used for comparison. The mortality rate was 59%. Septic CRRT patients had higher AOPP and lower %DR+ (p < 0.001, both) than healthy controls. They also had higher AOPP than septic patients who did not develop AKI (p < 0.001). No difference was found in AOPP, %DR+ and MFI between survivors and non-survivors (day 1 and subsequent measurements). No correlation was seen between severity scores and OS/HLA-DR. OS and HLA-DR expression are altered in septic patients with AKI undergoing CRRT. However, this study was not able to confirm the usefulness of these markers in predicting survival in this subset of patients.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 40%

Oxidative Stress and ‘Monocyte Reprogramming’ in Septic Patients with Acute Kidney Injury Requiring CRRT

Silva¹,

Cal²,

Cruz³

et al. 2008

Blood Purif

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“…In clinical studies, the magnitude and the persistent nature of this refractory state are associated with increased mortality. Two major consequences of endotoxin tolerance on monocytes are an increase in the release of immunosuppressive mediators, such as IL‐10, and a decrease in antigen presentation as a result of the reduced expression of human leukocyte antigen (HLA)‐DR; both are associated with a worse outcome of sepsis 20, 21. The continued release of IL‐10 might contribute to sepsis‐induced immunosuppression and thus might augment the susceptibility to secondary microbial infections 22.…”

Section: Mechanism Of Sepsis‐induced Immunosuppressionmentioning

confidence: 99%

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

Ono

Tsujimoto

Hiraki

et al. 2018

Annals of Gastroent Surgery

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Surgical injury can be a life‐threatening complication, not only due to the injury itself, but also due to immune responses to the injury and subsequent development of infections, which readily result in sepsis. Sepsis remains the leading cause of death in most intensive care units. Unfavorable outcomes of several high‐profile trials in the treatment of sepsis have led researchers to state that sepsis studies need a new direction. The immune response that occurs during sepsis is characterized by a cytokine‐mediated hyper‐inflammatory phase, which most patients survive, and a subsequent immunosuppressive phase. Therefore, therapies that improve host immunity might increase the survival of patients with sepsis. Many mechanisms are responsible for sepsis‐induced immunosuppression, including apoptosis of immune cells, increased regulatory T cells and expression of programmed cell death 1 on CD4+ T cells, and cellular exhaustion. Immunomodulatory molecules that were recently identified include interleukin‐7, interleukin‐15, and anti‐programmed cell death 1. Recent studies suggest that immunoadjuvant therapy is the next major advance in sepsis treatment.

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“…Reduced monocyte expression of the HLA class II DR molecule characterizes patients with septic shock with a poor prognosis, while recovery to normal is seen in those who survive. [16][17][18][19][20][21][22][23][24][25] The profound reduction in HLA-DR expression and a reduced ability in vitro to produce TNF-␣ following lipopolysaacharide stimulation is reflected in the fact that patients with septic shock usually succumb to repeated bacterial and opportunistic infections. 21 Recently, reduced monocyte HLA-DR expression has been reported in patients with septic decompensation of acute-on-chronic liver failure.…”

Section: S Ystemic Inflammatory Response Syndrome (Sirs) Ismentioning

confidence: 99%

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

et al. 2006

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Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-DR expression on monocytes is associated with disease severity and predicts outcome. We investigated monocyte HLA-DR expression in ALF in relation to inflammatory mediator levels and clinical outcome. Monocyte HLA-DR expression was determined in 50 patients with acetaminophen-induced ALF (AALF) and 20 non-acetaminophen-induced ALF (NAALF). AALF patients were divided into dead/transplanted (AALF-NS, n ‫؍‬ 26) and spontaneous survivors (AALF-S, n ‫؍‬ 24). Fifty patients with chronic liver disease (CLD) and 50 healthy volunteers served as controls. Monocyte HLA-DR expression was determined by double-color flow-cytometry with monoclonal antibodies detecting HLA-DR and monocyte specific CD14. Serum levels of interleukin (IL) -4, -6, -10, tumor necrosis factor (TNF)-␣ and interferon (IFN)-␥ were concomitantly measured by ELISA. Compared to healthy volunteers (75%) and CLD (67%) monocyte HLA-DR percentage expression was lower in AALF (15%, P < .001) and NAALF (22 %, P < .001). Compared to AALF-S, AALF-NS had lower monocyte HLA-DR % (11% vs. 36%, P < .001) and higher levels of IL-4, IL-6, IL-10 and TNF-␣ (P < .001). HLA-DR percentage negatively correlated with INR, blood lactate, pH and levels of encephalopathy (r ‫؍‬ ؊0.8 to ؊0.5, P < .01), IL-10 (r ‫؍‬ ؊0.8, P < .0001), TNF-␣ (r ‫؍‬ ؊0.4, P ‫؍‬ .02). HLA-DR percentage level <15% has a 96% sensitivity and 100% specificity and 98% accuracy in predicting poor prognosis. In conclusion, the strong relationship of monocyte HLA-DR expression with indices of disease severity, mediators of inflammation and outcome indicates a key role for this molecule as a biomarker of disease severity and prognosis. (HEPATOLOGY 2006;44:34-43.)

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Predictive Value of Monocyte Histocompatibility Leukocyte Antigen-DR Expression and Plasma Interleukin-4 and -10 Levels in Critically Ill Patients With Sepsis

Cited by 96 publications

References 0 publications

Oxidative Stress and ‘Monocyte Reprogramming’ in Septic Patients with Acute Kidney Injury Requiring CRRT

Oxidative Stress and ‘Monocyte Reprogramming’ in Septic Patients with Acute Kidney Injury Requiring CRRT

Mechanisms of sepsis‐induced immunosuppression and immunological modification therapies for sepsis

Reduced monocyte HLA-DR expression: A novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

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