High tumor necrosis factor serum level is associated with increased survival in patients with abdominal septic shock: A prospective study in 59 patients

Riché, F; Panís, Yves; Laisné, Marie-Josèphe; Briard, C; Cholley, Bernard; Bernard-Poenaru, Oana; Graulet, AM; Guéris, J; Valleur, Patrice

doi:10.1016/s0039-6060(96)80087-0

Cited by 56 publications

(21 citation statements)

References 25 publications

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“…From our previous experience with the macrophage sepsis model as well as from clinical observation, an “ideal response” is a consistent TNF reduction 10–40%. Reduced TNF levels (but not totally suppressed) are associated with best clinical outcome [44–48]. The percentile can easily be transformed to the actual value because the actual control value (pg/mL) for each experiment is given; for example, when the response is 80% of the control and the actual control value is 33,561 pg/mL, then the response is 0.8 × 33,561 pg/mL = 26,849 pg/mL.…”

Section: Methodsmentioning

confidence: 99%

Rapamycin Augments the NMDA-Mediated TNF Suppression of MRSA-Stimulated RAW264.7 Murine Macrophages

Spentzas

Shappley

Savorgnan

et al. 2012

International Journal of Inflammation

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Background. Methicillin-resistant Staphylococcus aureus (MRSA) can stimulate massive cytokine release. Ketamine suppresses tumor necrosis factor (TNF) secretion by MRSA-stimulated RAW264.7 macrophages, and the mechanism likely involves N-methyl-D-aspartic acid (NMDA) receptor antagonism. The downstream effects of NMDA-mediated TNF suppression, specifically the PI3K/Akt and mTOR modulation, have not been described. Methods. RAW264.7 cells were stimulated for 18 hrs with 105 to 107 CFU/mL inocula of either of two prototypical community-acquired- (CA-) MRSA isolates, USA300 strain LAC and USA400 strain MW2. Then we added the NMDA inhibitors ketamine or 2R-amino-5-phosphonopentanoate (AP5), NMDA substrate, LY294002, and rapamycin in various combinations. Results. NMDA inhibition suppressed TNF secretion by almost a third compared to the no-ketamine control. When NMDA substrate was added, the TNF secretion increased by 10%. Addition of LY294002 suppressed TNF production by macrophages by 20%. Rapamycin exhibited a concentration-dependent TNF induction-suppression response: induction at doses of 0.1 and 1 ng/mL and suppression at 10 and 100 ng/mL. Induction of TNF was abolished when LY294002 was added and the suppression became uniform. Ketamine-induced suppression of TNF secretion was intensified 10–15% when rapamycin was added, but not when LY294002 was added. Conclusion. These findings suggest that NMDA-induced TNF suppression can be augmented by concurrent mTOR inhibition.

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Section: Methodsmentioning

confidence: 99%

Rapamycin Augments the NMDA-Mediated TNF Suppression of MRSA-Stimulated RAW264.7 Murine Macrophages

Spentzas

Shappley

Savorgnan

et al. 2012

International Journal of Inflammation

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“…Various evidence has shown that high serum TNF-α levels were positively correlated with the severity and prognosis of inflammatory diseases [42, 43]. Data derived from in vitro and animal experiment data have indicated that the Fpr2/3 gene (an orthologue to human FPR2/ALX ) is crucial to enacting nonredundant functions including control of cell recruitment, phagocytosis, modulation of soluble mediator generation, and containment of bacteremia, which prevents spread to vital organs and opens new opportunities to manipulate the host response in sepsis.…”

Section: Discussionmentioning

confidence: 99%

The common promoter polymorphism rs11666254 downregulates FPR2/ALX expression and increases risk of sepsis in patients with severe trauma

Zhang

Sun

et al. 2017

Crit Care

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BackgroundFormyl peptide receptor 2-lipoxin receptor (FPR2/ALX) modulates the anti-inflammatory response and therefore may be a target for treating sepsis. The purpose of this study was to investigate the association between genetic variants of the FPR2/ALX gene and sepsis after severe trauma as well as to further analyze the functions of sepsis-related genetic polymorphisms.MethodsThree tag single-nucleotide polymorphisms (tag SNPs) that captured all common alleles across the FPR2/ALX genomic region were genotyped using pyrosequencing in an initial sample consisting of 275 patients with severe trauma. The rs11666254 polymorphism, which had statistical significance, was genotyped in an additional 371 patients, and logistic regression analysis was performed to determine associations between the FPR2/ALX gene polymorphism and sepsis susceptibility after severe trauma. The messenger RNA (mRNA) and protein levels of FPR2/ALX in the lipopolysaccharide-stimulated white blood cells of trauma patients were determined by performing quantitative polymerase chain reactions and Western blot analysis. Tumor necrosis factor (TNF)-α production was measured by enzyme-linked immunosorbent assay. The effects of the promoter polymorphism rs11666254 on the transcription activity of FPR2/ALX were analyzed using a luciferase reporter assay.ResultsAmong the three tag SNPs, only the rs11666254 polymorphism was found to be significantly associated with sepsis in trauma patients, and this association persisted after a pooled analysis of all 646 trauma patients, which showed that patients who carried the A allele of rs11666254 had a significantly higher risk of developing sepsis than individuals who carried the G allele. This SNP was also significantly associated with lower FPR2/ALX mRNA and protein expression as well as higher TNF-α production from the peripheral blood leukocyte response to bacterial lipoprotein stimulation. In addition, the rs11666254 polymorphism could significantly decrease the promoter activity of the FPR2/ALX gene.ConclusionsThe rs11666254 polymorphism in the FPR2/ALX gene is a functional SNP that increases sepsis susceptibility in patients after traumatic injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1757-3) contains supplementary material, which is available to authorized users.

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“…that IL-6 is not helpful in predicting mortality in peritonitis patients. [24][25][26] Controlling the septic source, peritoneal toilets and supportive measures such as fluid and antibiotic therapy certainly reverse the unfavorable peritoneal environment to a favorable one and restore a good recovery phase. A correlation between blood caspase levels and decrease in bacterial load in an animal model of peritonitis was shown before.…”

Section: Discussionmentioning

confidence: 99%

The value of CRP, IL-6, leptin, cortisol, and peritoneal caspase-3 monitoring in the operative strategy of secondary peritonitis

Pehlivanli¹,

Agalar²,

Ağalar³

et al. 2011

Ulus Travma Acil Cerrahi Derg

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High tumor necrosis factor serum level is associated with increased survival in patients with abdominal septic shock: A prospective study in 59 patients

Cited by 56 publications

References 25 publications

Rapamycin Augments the NMDA-Mediated TNF Suppression of MRSA-Stimulated RAW264.7 Murine Macrophages

Rapamycin Augments the NMDA-Mediated TNF Suppression of MRSA-Stimulated RAW264.7 Murine Macrophages

The common promoter polymorphism rs11666254 downregulates FPR2/ALX expression and increases risk of sepsis in patients with severe trauma

The value of CRP, IL-6, leptin, cortisol, and peritoneal caspase-3 monitoring in the operative strategy of secondary peritonitis

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