The effect of N-acetylcysteine on nuclear factor-κB activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis*

Paterson, Ross L; Galley, Helen F.; Webster, Nigel R.

doi:10.1097/01.ccm.0000089945.69588.18

Cited by 143 publications

(119 citation statements)

References 39 publications

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“…Thus, polymorphisms may exist in the Nrf2 gene that may identify subjects at risk for more severe sepsis. In a recent clinical trial, NAC was shown to reduce NF-κB activation as well as IL-8 secretion in patients with sepsis (19). However, in a subsequent randomized trial of 34 patients, NAC failed to improve end-organ function or microalbuminuria (20).…”

Section: Antioxidants and Sepsismentioning

confidence: 99%

Oxidative stress in sepsis: a redox redux

Kolls

2006

Journal of Clinical Investigation

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Section: Antioxidants and Sepsismentioning

confidence: 99%

Oxidative stress in sepsis: a redox redux

Kolls

2006

Journal of Clinical Investigation

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“…Neutrophils were immediately separated by single-step density gradient centrifugation, using Polymorphprep (AxisShield, Oslo, Norway) as previously described (16). The harvested cells were resuspended in RPMI 1640 culture medium supplemented with 10% heat-inactivated fetal calf serum, 20 mmol/liter L-glutamine, and 1% penicillin-streptomycin.…”

Section: Neutrophil Isolation Following Local Research Ethicsmentioning

confidence: 99%

Production of Soluble Triggering Receptor Expressed on Myeloid Cells by Lipopolysaccharide-Stimulated Human Neutrophils Involves De Novo Protein Synthesis

Mahdy

Lowes

Galley

et al. 2006

Clin Vaccine Immunol

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The triggering receptor expressed on myeloid cells (TREM-1) is a recently identified receptor expressed on neutrophils and monocytes. Activation of the receptor induces neutrophils to release the enzyme myeloperoxidase and inflammatory cytokines such as interleukin-8. TREM-1 has an alternatively spliced variant that lacks the transmembrane region, resulting in the receptor being secreted in a soluble form (sTREM-1). Soluble TREM-1 has been detected in plasma during experimental and clinical sepsis and has been advocated as a diagnostic marker of infection for pneumonia and as a prognostic marker for patients with septic shock. We studied TREM-1 surface expression, using flow cytometry, and simultaneously measured sTREM-1 concentrations in culture supernatants of lipopolysaccharide (LPS)-stimulated neutrophils. TREM-1 surface expression was constitutive and was not upregulated upon LPS stimulation. However, sTREM-1 release from neutrophils was significantly upregulated by LPS stimulation (P < 0.0001), an effect that was abrogated by cycloheximide. Soluble TREM-1 is therefore secreted by human neutrophils in response to LPS challenge in a process involving de novo protein synthesis that is not accompanied by an upregulation of the TREM-1 receptor on the surfaces of the cells.Despite advances in intensive care medicine, sepsis remains a major cause of morbidity and mortality, affecting more than 750,000 patients each year in Europe and the United States, with mortality ranging from 15% for uncomplicated sepsis to 80% for septic shock and multiple organ dysfunction syndrome (1,15).Neutrophils are activated as part of the host response to infection, and although protective in nature, this activation could lead to a wide range of pathological effects secondary to the release of inflammatory mediators, toxic substances, and oxidizing agents and through their interaction with endothelial cells (14,18). The triggering receptor expressed on myeloid cells (TREM-1) is a recently identified receptor expressed on neutrophils and a subset of monocytes. It is a member of the immunoglobulin (Ig) superfamily that contains a single Ig-like extracellular domain and a short cytoplasmic tail with no signaling motif. The transmembrane domain of TREM-1 has been shown to associate with the transmembrane adaptor protein DNAx activation protein 12 (DAP12), which in turn facilitates intracellular signal transduction (5). Triggering of the receptor induces neutrophils to release the enzyme myeloperoxidase and inflammatory cytokines such as interleukin-8 (IL-8). There is some evidence, though not consistent, that TREM-1 is upregulated on neutrophils upon exposure to lipopolysaccharide (LPS) (3). The importance of TREM-1 in the pathogenesis of sepsis was recently highlighted in murine models of sepsis, where the use of a TREM-1 decoy receptor downregulated the inflammatory response and protected mice from lethality (4).TREM-1 mRNA has an alternatively spliced variant which encodes a protein that lacks the transmembrane region, resulting in th...

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“…With this decrease in inflammatory mediators, end-organ stimulation such as the liver to release acute phase proteins decreases, thereby decreasing the stimulation of endothelial dysfunction, ultimately preventing plaque formation and the occurrence of atherosclerosis. 20,23,24 Overall benefit of this study was 2 x 600 mg oral NAS for eight weeks to reduce IL-6 levels in CKD stage V patients undergoing CAPD, so that the incidence of atherosclerosis can be decreased.…”

Section: Discussionmentioning

confidence: 99%

Oral N-Acetyl Cysteine Lowered IL 6 Level Among Stage V Chronic Kidney Disease Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD)

Nurhayatun

2017

JKKI

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(8,13 + 7,62 vs 11,16 + 8,32, p = 0,001), secara signifikan (p <0,001). Kadar IL 6 sebelum dan sesudah pengobatan pada kelompok perlakuan adalah (9,72 + 7,29 vs 6,09 + 3,82, p = 0,002); Menurun secara signifikan (p <0,05). Kesimpulan: Oral NAC menurunkan kadar IL 6 pada pasien CKD stadium V yang menjalani CAPD.Background: IL 6 level is increased in stage V CKD patients on CAPD. N-Acetyl Cysteine is a compound containing thiol with antioxidant and anti-inflammatory effects. Objective: To examine the effect of oral NAC on IL 6 level in stage V CKD patients on CAPD. Methods: An experimental research with Randomized Double Blind Control Trial, involving 30 CKD patients on CAPD in Dr Moewardi Hospital. They were divided into control group/placebo (15 patients) and oral NAS treatment group (15 patients). IL 6 level was measured before and after 8 weeks of treatment. Results : Level of IL 6 before and after treatment in control group were (8.13 + 7.62 vs 11.16 + 8.32 , p= 0,001), significantly (p<0,001). Level of IL 6 before and after treatment in treatment group were (9.72 + 7.29 vs 6.09 + 3.82, p = 0,002); lowered significantly (p<0,05). Conclusion: Oral NAC lowered the level of IL 6 in stage V CKD patients on CAPD.

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The effect of N-acetylcysteine on nuclear factor-κB activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis*

Cited by 143 publications

References 39 publications

Oxidative stress in sepsis: a redox redux

Oxidative stress in sepsis: a redox redux

Production of Soluble Triggering Receptor Expressed on Myeloid Cells by Lipopolysaccharide-Stimulated Human Neutrophils Involves De Novo Protein Synthesis

Oral N-Acetyl Cysteine Lowered IL 6 Level Among Stage V Chronic Kidney Disease Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD)

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