Burn Trauma Induces Early Hmgb1 Release in Patients

Lantos, János; Foldi, V.; Röth, Elizabeth; Weber, G; Bogár, Lajos; Csontos, Csaba

doi:10.1097/shk.0b013e3181cd8c88

Cited by 58 publications

(46 citation statements)

References 32 publications

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“…High-mobility group box 1 levels are increased in patients with community-acquired pneumonia (14), severe burns (15, 16), sepsis (17), or pancreatitis (18). Recently, we reported that persistent HMGB1 elevation after CLP is sufficient to induce immune dysregulation (splenomegaly, leukocytosis, and splenocyte priming) lasting for at least 8 weeks after onset of sepsis (8).…”

Section: Discussionmentioning

confidence: 99%

High-Mobility Group Box 1 Mediates Persistent Splenocyte Priming in Sepsis Survivors

Valdés‐Ferrer

Rosas-Ballina

Olofsson

et al. 2013

Shock

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Severe sepsis is a life-threatening complication of infection and injury affecting more than 700,000 people in the United States each year. Two thirds of patients with severe sepsis will survive to be discharged. Survivors have high incidence of cognitive impairment, immune dysregulation, functional impairments with marked disability, and 5-year mortality rates of 82%. High-mobility group box 1 (HMGB1) is necessary and sufficient mediator of sepsis pathogenesis in experimental models of this syndrome. The spleen is a crucial organ in the immune response to severe infection, and splenocyte dysfunction occurs in sepsis survivors. We hypothesized that HMGB1 plays a key role in mediating the immune dysfunction of splenocytes in sepsis survivors. Mice that survived cecal ligation and puncture–induced sepsis develop persistent splenomegaly; furthermore, splenocytes derived from sepsis survivors had enhanced responses to lipopolysaccharide ex vivo. Administration of neutralizing anti-HMGB1 antibody to sepsis survivors attenuated development of splenomegaly and reversed splenocyte priming. Splenocytes exposed to HMGB1 and subsequently challenged with cognate ligands to Toll-like receptor 2 (TLR2,) TLR4, TLR9, and RAGE (receptor for advanced glycation end product) receptors had enhanced cytokine release as compared with splenocytes not previously exposed to HMGB1. Exposure of TLR2−/−, TLR9−/−, or RAGE−/− splenocytes to HMGB1 enhanced responses to other TLR receptor ligands; in contrast, HMGB1 failed to prime TLR4−/− splenocytes. These findings indicate that exposure to HMGB1 enhances splenocyte responses to secondary inflammatory challenges, a priming effect dependent on TLR4, and that anti-HMGB1 monoclonal antibody may be beneficial in sepsis survivors.

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Section: Discussionmentioning

confidence: 99%

High-Mobility Group Box 1 Mediates Persistent Splenocyte Priming in Sepsis Survivors

Valdés‐Ferrer

Rosas-Ballina

Olofsson

et al. 2013

Shock

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“…Some studies reported that the IL-6 concentration was highest at 1 day after the burn, and then decreased [9], whereas other studies reported that it was highest after 3-4 days [1, 3, 7, 20, 21]. Similarly, IL-8 concentration has been reported as highest after 1 day, followed by a decrease [17], but also as highest after 3-4 days [1, 20, 21] or after 15-21 days [3].…”

Section: Discussionmentioning

confidence: 99%

Changes in the Levels of Interleukins 6, 8, and 10, Tumor Necrosis Factor Alpha, and Granulocyte-colony Stimulating Factor in Korean Burn Patients: Relation to Burn Size and Postburn Time

Kim

Yim

et al. 2012

Ann Lab Med

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BackgroundMajor burn injury induces an inflammatory response that is accompanied by the release of various cytokines. We investigated the gradual changes in the levels of pro-inflammatory and anti-inflammatory cytokines following burn injury and determined the relationship between these levels and burn size in adult Korean patients with burn injury.MethodsBlood samples from 9 healthy controls and 60 Korean burn patients were collected on days 1, 3, 7, 14, and 21 after burn injury, and concentrations of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF) were measured. Burn patients were divided into 3 groups according to burn size (15-30%, 31-50%, >50% total body surface area), and the concentrations of the cytokines were compared between these groups and the control group over 3 weeks.ResultsCompared to their levels in controls, IL-6, IL-8, IL-10, TNF-α, and G-CSF levels in burn patients were significantly higher during the observation period. Median concentrations of IL-8, IL-10, and G-CSF at each time point increased with burn size, although peak levels and time to peak levels of these cytokines differed from patient to patient.ConclusionsThese findings indicate that IL-6, IL-8, IL-10, TNF-α, and G-CSF are important mediators in inflammatory changes after burn injury; however, various factors, including burn size, may influence the concentrations of these cytokines.

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“…HMGB1 is a nuclear protein that may be released actively from monocytes and macrophages or passively from necrotic or damaged cells. The HMGB1 levels are increased upon patients’ admission in parallel with IL-10 increase and highly associated with following induction of IL-8 and IL-6 [21]. In a 20% full thickness burn rodent model, Cairns et al examined the cytokine secretion profile of purified splenic macrophage in response to TLR2 ligand peptidoglycan or TLR4 ligand LPS.…”

Section: Perturbed Mps In Severely Burned Patientsmentioning

confidence: 99%

Perturbed Mononuclear Phagocyte System in Severely Burned and Septic Patients

Xiu

Jeschke

2013

Shock

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Burn is one of the most common and devastating forms of trauma. Major burn injury disturbs the immune system, resulting in marked alterations in bone marrow hematopoiesis and a progressive suppression of the immune response, which are thought to contribute to increased susceptibility to secondary infections and the development of sepsis. Immunosuppression in severely burned and septic patients leads to high morbidity and mortality in these patients. Mononuclear Phagocytes System (MPS) is a critical component of the innate immune response and play key roles in burn immunity. These phagocytes are the first cellular responders to severe burn injury after acute disruption of the skin barrier. They are not only able to internalize and digest bacteria and dead cells and scavenge toxic compounds produced by metabolism, but also able to initiate an adaptive immune response. Severe burn and sepsis profoundly inhibit the functions of DC, monocyte and macrophage. Adoptive transfer of MPS or stem cells to severely burned and septic patients that aim to restore MPS function is promising. A better understanding of the roles played by MPS in the pathophysiology of severe burn and sepsis will guarantee a more rational and effective immunotherapy of severely burned and septic patients.

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Burn Trauma Induces Early Hmgb1 Release in Patients

Cited by 58 publications

References 32 publications

High-Mobility Group Box 1 Mediates Persistent Splenocyte Priming in Sepsis Survivors

High-Mobility Group Box 1 Mediates Persistent Splenocyte Priming in Sepsis Survivors

Changes in the Levels of Interleukins 6, 8, and 10, Tumor Necrosis Factor Alpha, and Granulocyte-colony Stimulating Factor in Korean Burn Patients: Relation to Burn Size and Postburn Time

Perturbed Mononuclear Phagocyte System in Severely Burned and Septic Patients

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