Systemic and local high mobility group box 1 concentrations during severe infection

Zoelen, Marieke A. D. van; Laterre, Pierre‐François; Veen, Suzanne Q. van; Till, J. W. Olivier van; Wiffebole, Xavier; Bresser, Paul; Tanck, Michael W.T.; Dugernier, Thierry; Ishizaka, Akitoshi; Boermeester, Marja A.; Poll, Tom van der

doi:10.1097/01.ccm.0000287588.69000.97

Cited by 75 publications

(48 citation statements)

References 35 publications

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“…We previously demonstrated increased HMGB1 concentrations in BALF from the infected site of patients with pneumonia (van Zoelen et al, 2007), with S. pneumoniae being isolated in 3 out of 4 cases. Relative to healthy controls, mice with pneumonia induced by IAV had elevated HMGB1 levels in BALF at day 4 and day 8 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Receptor for advanced glycation end products is detrimental during influenza A virus pneumonia

Zoelen¹,

Sluijs²,

Achouiti³

et al. 2009

Virology

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Pneumonia caused by influenza A virus (IAV) can have devastating effects, resulting in respiratory failure and death. The idea that a new influenza pandemic might occur in the near future has triggered renewed interests in IAV infection. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory processes. We here investigated the role of RAGE in the host response to IAV pneumonia using wild-type (wt) and RAGE deficient (−/−) mice. Whereas strong RAGE was constitutively expressed in the lungs of uninfected wt mice, in particular on endothelium, IAV pneumonia was associated with enhanced expression on endothelium and de novo expression on bronchial epithelium. Additionally, the high-affinity RAGE ligand high mobility group box 1 was upregulated during IAV pneumonia. RAGE−/− mice were relatively protected from IAV induced mortality and showed an improved viral clearance and enhanced cellular T cell response and activation of neutrophils. These data suggest that RAGE is detrimental during IAV pneumonia.

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Section: Resultsmentioning

confidence: 99%

Receptor for advanced glycation end products is detrimental during influenza A virus pneumonia

Zoelen¹,

Sluijs²,

Achouiti³

et al. 2009

Virology

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“…We recently reported that patients with peritonitis showed strongly elevated HMGB-1 concentrations in their abdominal fluid (5). Therefore, we here chose to administer HMGB-1 intraperitoneally to more closely mimic a possible clinical scenario of an (initially) localized infection.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, dying of these mice paralleled the accumulation of systemic HMGB-1, and postponed treatment with an anti–HMGB-1 antibody protected against lethality caused by high-dose LPS administration or cecal ligation and puncture in mice (2, 3). Moreover, clinical observational studies have further implicated HMGB-1 as a late mediator of sepsis: patients with severe sepsis have elevated HMGB-1 concentrations in their circulation (2, 4, 5). In addition, we recently reported that patients with peritonitis have greater than 10-fold higher HMGB-1 concentrations in their abdominal fluid than in concurrently obtained plasma, suggesting that this mediator is released locally at the site of infection (5).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, clinical observational studies have further implicated HMGB-1 as a late mediator of sepsis: patients with severe sepsis have elevated HMGB-1 concentrations in their circulation (2, 4, 5). In addition, we recently reported that patients with peritonitis have greater than 10-fold higher HMGB-1 concentrations in their abdominal fluid than in concurrently obtained plasma, suggesting that this mediator is released locally at the site of infection (5). …”

Section: Introductionmentioning

confidence: 99%

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Role of Toll-Like Receptors 2 and 4, and the Receptor for Advanced Glycation End Products in High-Mobility Group Box 1-Induced Inflammation in Vivo

Zoelen¹,

Yang

Florquin³

et al. 2009

Shock

246

186

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High-mobility group box 1 (HMGB-1) has been reported as a “late” proinflammatory mediator in sepsis. In vitro data have shown that HMGB-1 can induce activation of intracellular signaling pathways via interaction with at least three pattern recognition receptors: Toll-like receptor (TLR) 2, TLR-4, and the receptor for advanced glycation end products (RAGE). The objective of this study was to investigate the role of these receptors in the in vivo response to HMGB-1. Therefore, we first performed a time-series experiment with wild-type (Wt) mice. High-mobility group box 1 induced time-dependent elevations of TNF-α, IL-6, monocyte chemoattractant protein 1, and thrombin-antithrombin complex levels in peritoneal lavage fluid and plasma. This inflammatory reaction was accompanied by a prominent and sustained rise in neutrophil counts in the peritoneal cavity. We next administered HMGB-1 to Wt, TLR-2−/−, TLR-4−/−, and RAGE−/− mice. All genotypes showed similar plasma levels of TNF-α, IL-6, IL-10, and thrombin-antithrombin complex at 2 h after intraperitoneal injection of HMGB-1. Compared with Wt mice, both TLR-4−/− and RAGE−/− mice displayed lower TNF-α and IL-6 concentrations and lower neutrophil numbers in their peritoneal lavage fluid. In contrast, TLR-2−/− mice showed increased levels of TNF-α and IL-6 in their peritoneal cavity relative to Wt mice. These data indicate that HMGB-1 induces release of cytokines, activation of coagulation, and neutrophil recruitment in vivo via a mechanism that at least in part depends on TLR-4 and RAGE.

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“…More recently, HMGB-1 has been found to act as a "late" inflammatory cytokine that contributes to the pathological progression of sepsis and other inflammatory disorders (36). In patients with severe sepsis, the kinetic of circulating HMGB1 may differ from the classic mouse model findings depending on the primary source of infection (37). HMGB-1 has been proven to be a successful therapeutic target in experimental models of diverse infectious and inflammatory diseases (39).…”

Section: Discussionmentioning

confidence: 99%

Caracterización de la expresión de nCD64 en neutrófilos y de los niveles de s-TREM-1 y HMGB-1 en pacientes con sospecha de infección admitidos en el departamento de emergencias

et al. 2013

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Introduction:The nCD64 receptor, the soluble triggering receptor expressed in myeloid cells (s-TREM-1), and the high mobility group-box 1 protein (HMGB-1) have been proposed as significant mediators in sepsis. Objective: To evaluate the prognostic value of these markers in patients with suspected infection recently admitted in an emergency department (ED). Materials and methods:All patients who presented to the ED with suspected infection were eligible for enrollment in this study. Baseline clinical data, Sequential Organ Failure Assessment score (SOFA) score, APACHE II score, HMGB-1 levels, s-TREM-1 levels, and nCD64 levels were analyzed. The HMGB-1 and sTREM-1 serum concentrations were determined using commercially available ELISA kits, and CD64 on the surface of neutrophils was measured by flow cytometry. Results:. A total of 579 patients with suspected infection as their admission diagnosis were enrolled in this study. The median patient age was 50 years (IQR = 35-68). Morbidity during the 28-day followup period was 11.1% (n=64). The most frequent diagnosis at the time of admission was communityacquired pneumonia (CAP) in 23% (n=133) patients, followed by soft tissue infection in 16.6% (n=96), and urinary tract infection in 15% (n=87). After multivariable analysis, no significant association was identified between any biomarker and 28-day mortality. Conclusion:In the context of a tertiary care hospital emergency department in a Latin-American city, the nCD64 receptor, s-TREM-1, and HMGB-1 biomarkers do not demonstrate prognostic utility in the management of patients with infection. The search continues for more reliable prognostic markers in the early stages of infection.

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Systemic and local high mobility group box 1 concentrations during severe infection

Abstract: In severe sepsis, the kinetics of HMGB1 release may differ depending on the primary source of infection. In patients with severe infection, HMGB1 release may predominantly occur at the site of infection.

Cited by 75 publications

References 35 publications

Receptor for advanced glycation end products is detrimental during influenza A virus pneumonia

Receptor for advanced glycation end products is detrimental during influenza A virus pneumonia

Role of Toll-Like Receptors 2 and 4, and the Receptor for Advanced Glycation End Products in High-Mobility Group Box 1-Induced Inflammation in Vivo

Caracterización de la expresión de nCD64 en neutrófilos y de los niveles de s-TREM-1 y HMGB-1 en pacientes con sospecha de infección admitidos en el departamento de emergencias

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