New concepts in sepsis

Sessler, Curtis N.; Shepherd, Wes

doi:10.1097/00075198-200210000-00016

Cited by 55 publications

(50 citation statements)

References 68 publications

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“…Cardiac dysfunction during sepsis (12,22) is associated with poor outcome in both humans (2,40) and animals (7,11). We and others (19,21,23) have previously demonstrated that sepsis-or burn-associated cardiac dysfunction is primarily due to circulating myocardial depressant factors, including TNF-␣.…”

Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor

Garner

Willis

Carlson

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Macrophage migration inhibitory factor (MIF) is a pluripotent proinflammatory cytokine that is ubiquitously expressed in organs, including the heart. However, no specific role for MIF in modulating cardiac performance has yet been described. Therefore, we examined cardiac MIF expression in mice after LPS challenge (4 mg/kg) and tested the hypothesis that MIF is a mediator of LPS-induced cardiac dysfunction. Western blots of whole heart lysates, as well as immunohistochemistry, documented constitutive MIF protein expression in the heart. Cardiac MIF protein levels significantly decreased after LPS challenge, reaching a nadir at 12 h, and then returned to baseline by 24 h. This pattern was consistent with MIF release from cytoplasmic stores after endotoxin challenge. After release of protein, MIF mRNA levels increased 24–48 h postchallenge. To determine the functional consequences of MIF release, we treated LPS-challenged mice with anti-MIF neutralizing antibodies or isotype control antibodies. Anti-MIF-treated animals had significantly improved cardiac function, as evidenced by a significant improvement in left ventricular (LV) fractional shortening percentage at 8, 12, 24, and 48 h after endotoxin challenge. In support of these findings, perfusion of isolated beating mouse hearts (Langendorff preparation) with recombinant MIF (20 ng/ml) led to a significant decrease in both systolic and diastolic performance [LV pressure (LVP), positive and negative first derivative of LVP with respect to time, and rate of LVP rise at developed pressure of 40 mmHg]. This study demonstrates that MIF mediates LPS-induced cardiac dysfunction and suggests that MIF should be considered a pharmacological target for the treatment of cardiac dysfunction in sepsis and potentially other cardiac diseases.

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Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor

Garner

Willis

Carlson

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…Despite the recent advances in intensive care treatment and the discovery of antibiotics, sepsis remains associated with a high mortality rate (1,2). Sepsis is commonly initiated by an infection, but its pathogenesis is characterized by an overwhelming systemic inflammatory response and subsequent immune dysfunction, which can lead to lethal multiple organ failure (3).…”

mentioning

confidence: 99%

Bacterial Endotoxin Induces the Release of High Mobility Group Box 1 via the IFN-β Signaling Pathway

Kim

Lee

et al. 2009

The Journal of Immunology

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Sepsis is a devastating condition characterized by a systemic inflammatory response. Recently, high mobility group box 1 (HMGB1) was identified as a necessary and sufficient mediator of the lethal systemic inflammation caused by sepsis. However, despite its clinical importance, the mechanism of HMGB1 release has remained to be elusive. In this study, we demonstrate that the IFN-β-mediated JAK/STAT pathway is essential for LPS or Escherichia coli-induced HMGB1 release, which is dependent on Toll/IL-1R domain-containing adapter-inducing IFN-β adaptor. Additionally, we show that NO acts as a downstream molecule of the IFN-β signaling. Furthermore, the JAK inhibitor treatment as well as the STAT-1 or IFN-β receptor deficiency reduced HMGB1 release in a murine model of endotoxemia. Our results suggest that HMGB1 release in sepsis is dependent on the IFN-β signaling axis; thus, therapeutic agents that selectively inhibit IFN-β signaling could be beneficial in the treatment of sepsis.

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“…Despite the recent advances in intensive care treatment and the discovery of antibiotics, sepsis remains associated with a high mortality rate (1,2). Although commonly initiated by an infection, the pathogenesis of sepsis is characterized by an overwhelming systemic inflammatory response and subsequent immune dys-function, which can lead to lethal multiple organ failure (3).…”

Section: Introductionmentioning

confidence: 99%

Sepsis Mortality in CIITA Deficient Mice is Associated with Excessive Release of High-mobility Group Box 1

Kim

Seo

et al. 2008

Immune Netw

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New concepts in sepsis

Cited by 55 publications

References 68 publications

Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor

Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor

Bacterial Endotoxin Induces the Release of High Mobility Group Box 1 via the IFN-β Signaling Pathway

Sepsis Mortality in CIITA Deficient Mice is Associated with Excessive Release of High-mobility Group Box 1

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