Blood interleukin 10 levels parallel the severity of septic shock

Friedman, Gilberto; Jankowski, S.; Marchant, Arnaud; Goldman, Michel; Kahn, Robert J.; Vincent, Jean‐Louis

doi:10.1016/s0883-9441(97)90030-7

Cited by 106 publications

(48 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The latter group revealed a much more modest consumption of complement (Table II). This finding is in accord with a previous report on 11 patients in septic shock, in whom lower CH50 values were observed and were associated with a higher organ failure score (36). For the anaphylatoxin C5a, previous studies either found C5a below the detection limit in serum (33) or suggested that most C5a generated was bound to circulating leukocytes in plasma (31) and therefore not detectable.…”

Section: Discussionsupporting

confidence: 91%

Changes and Regulation of the C5a Receptor on Neutrophils during Septic Shock in Humans

Unnewehr

Rittirsch

Sarma

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

During experimental sepsis, excessive generation of the anaphylatoxin C5a results in reduction of the C5a receptor (C5aR) on neutrophils. These events have been shown to result in impaired innate immunity. However, the regulation and fate of C5aR on neutrophils during sepsis are largely unknown. In contrast to 30 healthy volunteers, 60 patients in septic shock presented evidence of complement activation with significantly increased serum levels of C3a, C5a, and C5b-9. In the septic shock group, the corresponding decrease in complement hemolytic activity distinguished survivors from nonsurvivors. Neutrophils from patients in septic shock exhibited decreased C5aR expression, which inversely correlated with serum concentrations of C-reactive protein (CRP) and clinical outcome. In vitro exposure of normal neutrophils to native pentameric CRP led to a dose- and time-dependent loss of C5aR expression on neutrophils, whereas the monomeric form of CRP, as well as various other inflammatory mediators, failed to significantly alter C5aR levels on neutrophils. A circulating form of C5aR (cC5aR) was detected in serum by immunoblotting and a flow-based capture assay, suggestive of an intact C5aR molecule. Levels of cC5aR were significantly enhanced during septic shock, with serum levels directly correlating with lethality. The data suggest that septic shock in humans is associated with extensive complement activation, CRP-dependent loss of C5aR on neutrophils, and appearance of cC5aR in serum, which correlated with a poor outcome. Therefore, cC5aR may represent a new sepsis marker to be considered in tailoring individualized immune-modulating therapy.

show abstract

Section: Discussionsupporting

confidence: 91%

Changes and Regulation of the C5a Receptor on Neutrophils during Septic Shock in Humans

Unnewehr

Rittirsch

Sarma

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…[1][2][3] Recent data suggest that circulating levels of the antiinflammatory cytokine IL-10 also correlate with the severity of the systemic inflammatory insult. 4,5 The evidence to date indicates that there is a complex interaction between pro-and anti-inflammatory responses during the evolution of this inflammatory process.…”

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

View full text Add to dashboard Cite

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.)

show abstract

“…Besides stimulating the synthesis of proinflammatory cytokines, the septic response in patients and animal models also results in the production of antiinflammatory mediators, such as IL-10 (8,11,30,31). IL-10 is a 35-kDa homodimeric protein, produced primarily by monocytes, T cells, and B cells, that inhibits the production of proinflammatory cytokines in vitro (16).…”

mentioning

confidence: 99%

Interleukin-10 Controls the Onset of Irreversible Septic Shock

Latifi¹,

O’Riordan²,

2002

View full text Add to dashboard Cite

Lethality from sepsis is believed to be mediated by a proinflammatory cytokine cascade, yet blocking the proinflammatory cytokines tumor necrosis factor alpha (TNF-␣) and interleukin-1 (IL-1) fails to prevent mortality in human disease and a mouse model of sepsis induced by cecal ligation and puncture (CLP). The role of the antiinflammatory cytokine IL-10 in the CLP model of sepsis is unclear, with either protective or harmful effects demonstrated, depending upon the time of intervention. We therefore hypothesize that IL-10 functions as a temporal regulator of the transition from early reversible sepsis to the late phase of irreversible shock. Transition from reversible sepsis to irreversible shock in the CLP model was defined as the time when removal of the necrotic cecum by rescue surgery is no longer effective. We subjected IL-10-deficient (IL-10 ؊/؊ ) and wild-type (IL-10 ؉/؉ ) mice to CLP and monitored the progression of sepsis, the onset of irreversible shock, and mortality. Onset of lethality in IL-10 ؊/؊ mice occurred significantly earlier than in IL-10 ؉/؉ mice and was associated with 15-fold-higher serum levels of TNF-␣ and IL-6. Consistent with these findings, the efficacy of rescue surgery after lethal CLP is lost 10 h earlier in IL-10 ؊/؊ mice than in IL-10 ؉/؉ mice. Treatment with recombinant human IL-10 5 h after CLP significantly improved survival and lengthened the therapeutic window for rescue surgery in both strains of mice. These results demonstrate that IL-10 controls the onset of irreversible septic shock after CLP.

show abstract

Blood interleukin 10 levels parallel the severity of septic shock

Cited by 106 publications

References 34 publications

Changes and Regulation of the C5a Receptor on Neutrophils during Septic Shock in Humans

Changes and Regulation of the C5a Receptor on Neutrophils during Septic Shock in Humans

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

Interleukin-10 Controls the Onset of Irreversible Septic Shock

Contact Info

Product

Resources

About