Administration of Anti-TNF Antibody Improves Left Ventricular Function in Septic Shock Patients

Vincent, Jean‐Louis; Bakker, Jan; Marécaux, Gaëtan; Schandené, Liliane; Kahn, Robert J.; Dupont, Étienne

doi:10.1378/chest.101.3.810

Cited by 209 publications

(85 citation statements)

References 31 publications

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“…Both these latter cytokines depressed myocardial contractility in vitro or ex vivo (16,28). Moreover, the neutralization or removal of TNF-␣ or IL-1␤ from human septic serum partly abrogates the myocardial depressant effect in vitro and in vivo (20,27). Although P1 and LP17 had an identical action on blood flows and arterial pressure during endotoxemia, their action on cytokine production differed with only a slight effect of P1 on TNF-␣ and IL-1␤ concentrations in plasma.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the Triggering Receptor Expressed on the Myeloid Cell Type 1 Pathway in Murine Septic Shock

Gibot¹,

et al. 2006

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The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell surface molecule that has been identified on both human and murine polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in the presence of microbial components amplifies the inflammatory response and may be responsible for the hyperresponsiveness observed during the initial stage of sepsis. To investigate the effect of the modulation of the TREM-1 pathway during experimental murine sepsis, we used analogue synthetic peptides derived from the extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both peritoneal and peripheral neutrophils during experimental peritonitis in mice. The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and protected endotoxinic mice from death. In septic rats, the TREM-1 peptides improved the hemodynamic status, attenuated the development of lactic acidosis, modulated the production of such proinflammatory cytokines as tumor necrosis factor alpha and interleukin-1␤, and improved survival. The protective effect of these peptides on arterial pressure could partly be explained by a decreased production of nitric oxide. These data suggest that in vivo modulation of TREM-1 might be a suitable therapeutic tool for the treatment of sepsis.

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Section: Discussionmentioning

confidence: 99%

Modulation of the Triggering Receptor Expressed on the Myeloid Cell Type 1 Pathway in Murine Septic Shock

Gibot¹,

et al. 2006

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“…This is consistent with the beneficial activity of similar doses of anti-TNF-a antibodies in models of septic shock in mice (Silva et al, 1990), pigs (Windsor et al, 1994) and monkeys (Fiedler et al, 1992). In human sepsis, anti TNF-a therapy did not clearly improve survival (see Natanson et al, 1994), although positive clinical data have been obtained (Vincent et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

The contribution of tumour necrosis factor‐α and endothelin‐1 to the increase of coronary resistance in hearts from rats treated with endotoxin

Hohlfeld

Klemm

Thiemermann

et al. 1995

British J Pharmacology

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1 Inflammatory disease states predispose to myocardial infarction. Here we have investigated the effects of a systemic inflammatory response syndrome, i.e. lipopolysaccharide (LPS)-induced circulatory shock in rats, on coronary vascular tone. 2 Anaesthetized rats were given LPS (10 mg kg-', i.v.) and the hearts excised 180 min later for isolated perfusion at constant flow by the Langendorff technique. Once the ex vivo perfusion was started, the perfusion pressure strongly increased in these hearts compared to hearts from control rats (130+3 vs. 49+3 mmHg after 10 min). This increase in coronary resistance was not associated with a reduction in endothelial cell function, for the vasodilator responses to bradykinin were unchanged. 3 When hearts were removed 30 min after the injection of LPS, the LPS-induced rise in perfusion pressure was delayed. No changes in perfusion pressure were seen when the hearts were removed 15 min after the injection of LPS. Pre-treatment with cycloheximide or an anti-tumour necrosis factor-a (TNF-a) antibody or continuous infusion in vivo and in vitro of the endothelin ETA receptor selective antagonist FR 139317, greatly decreased the increase in coronary vascular resistance induced by LPS. 4 These data suggest that TNF-cx may induce the release of endothelin-1 (ET-1) and that this mediates at least part of the coronary vasoconstriction. This hypothesis is supported by the demonstration that LPS administration increased the circulating levels of both TNF-a and ET-1. 5 We conclude, therefore, that in inflammatory disease states, such as LPS-induced septic shock, there is the sequential release of TNF-a and endothelin-1 which leads to an increase in coronary vascular tone and so a predisposition to myocardial ischaemia. Inactivation of TNF-a by an antibody as well as ETA receptor blockade by a selective antagonist may effectively interfere with this pathway.

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“…For example, TNF-α and IL-1β are 2 potent proinflammatory cytokines released by macrophages in sepsis that have each demonstrated in vitro depression of cardiac contractility [33,34]. A trial conducted in the early 1990s on 10 patients with refractory septic shock using a monoclonal TNF-α antibody (Ab) revealed a transient but statistically significant decrease in heart rate and increase in left ventricular stroke-work index [35]. Nevertheless, no large scale clinical trials have shown a mortality benefit with TNF-α Ab in septic shock [4].…”

Section: Other Cytokine Effectsmentioning

confidence: 99%

Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms

2010

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Administration of Anti-TNF Antibody Improves Left Ventricular Function in Septic Shock Patients

Cited by 209 publications

References 31 publications

Modulation of the Triggering Receptor Expressed on the Myeloid Cell Type 1 Pathway in Murine Septic Shock

Modulation of the Triggering Receptor Expressed on the Myeloid Cell Type 1 Pathway in Murine Septic Shock

The contribution of tumour necrosis factor‐α and endothelin‐1 to the increase of coronary resistance in hearts from rats treated with endotoxin

Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms

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