Soluble ST2 levels are associated with bleeding in patients with severe Leptospirosis

Severe leptospirosis features bleeding and multi-organ failure, leading to shock and death. Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis. Indeed, several proinflammatory cytokines are reported to be induced during leptospirosis....

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Veröffentlicht in:PLoS neglected tropical diseases 2009-06, Vol.3 (6), p.e453-e453
Hauptverfasser: Wagenaar, Jiri F P, Gasem, M Hussein, Goris, Marga G A, Leeflang, Mariska, Hartskeerl, Rudy A, van der Poll, Tom, van 't Veer, Cornelis, van Gorp, Eric C M
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container_end_page e453
container_issue 6
container_start_page e453
container_title PLoS neglected tropical diseases
container_volume 3
creator Wagenaar, Jiri F P
Gasem, M Hussein
Goris, Marga G A
Leeflang, Mariska
Hartskeerl, Rudy A
van der Poll, Tom
van 't Veer, Cornelis
van Gorp, Eric C M
description Severe leptospirosis features bleeding and multi-organ failure, leading to shock and death. Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis. Indeed, several proinflammatory cytokines are reported to be induced during leptospirosis. Toll-like receptors, which play an important role in the initiation of an innate immune response, are inhibited by negative regulators including the membrane-bound ST2 (mST2) receptor. Soluble ST2 (sST2) has been implicated to inhibit signaling through mST2. The aim of this study was to determine the extent of sST2 and (pro-) inflammatory cytokine release in patients with severe leptospirosis. In an observational study, 68 consecutive cases of severe leptospirosis were included. Soluble ST2 and cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10) were repeatedly measured. To determine whether blood cells are a source of sST2 during infection, we undertook an in vitro experiment: human whole blood and peripheral blood mononuclear cells (PBMC) were stimulated with viable pathogenic Leptospira. All patients showed elevated sST2, IL-6, IL-8, and IL-10 levels on admission. Admission sST2 levels correlated with IL-6, IL-8, and IL-10. Thirty-four patients (50%) showed clinical bleeding. Soluble ST2 levels were significantly associated with bleeding overall (OR 2.0; 95%CI: 1.2-3.6) and severe bleeding (OR 5.1; 95%CI: 1.1-23.8). This association was unique, since none of the cytokines showed this correlation. Moreover, sST2 was associated with mortality (OR 2.4; 95%CI: 1.0-5.8). When either whole blood or isolated PBMCs were stimulated with Leptospira in vitro, no sST2 production could be detected. Patients with severe leptospirosis demonstrated elevated plasma sST2 levels. Soluble ST2 levels were associated with bleeding and mortality. In vitro experiments showed that (white) blood cells are probably not the source. In this regard, sST2 could be an indicative marker for tissue damage in patients suffering from severe leptospirosis.
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Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis. Indeed, several proinflammatory cytokines are reported to be induced during leptospirosis. Toll-like receptors, which play an important role in the initiation of an innate immune response, are inhibited by negative regulators including the membrane-bound ST2 (mST2) receptor. Soluble ST2 (sST2) has been implicated to inhibit signaling through mST2. The aim of this study was to determine the extent of sST2 and (pro-) inflammatory cytokine release in patients with severe leptospirosis. In an observational study, 68 consecutive cases of severe leptospirosis were included. Soluble ST2 and cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10) were repeatedly measured. To determine whether blood cells are a source of sST2 during infection, we undertook an in vitro experiment: human whole blood and peripheral blood mononuclear cells (PBMC) were stimulated with viable pathogenic Leptospira. All patients showed elevated sST2, IL-6, IL-8, and IL-10 levels on admission. Admission sST2 levels correlated with IL-6, IL-8, and IL-10. Thirty-four patients (50%) showed clinical bleeding. Soluble ST2 levels were significantly associated with bleeding overall (OR 2.0; 95%CI: 1.2-3.6) and severe bleeding (OR 5.1; 95%CI: 1.1-23.8). This association was unique, since none of the cytokines showed this correlation. Moreover, sST2 was associated with mortality (OR 2.4; 95%CI: 1.0-5.8). When either whole blood or isolated PBMCs were stimulated with Leptospira in vitro, no sST2 production could be detected. Patients with severe leptospirosis demonstrated elevated plasma sST2 levels. Soluble ST2 levels were associated with bleeding and mortality. 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subjects Adult
Critical Care and Emergency Medicine/Sepsis and Multiple Organ Failure
Cytokines
Cytokines - blood
Female
Hemorrhage - parasitology
Humans
Immune system
Immunology
Immunology/Immune Response
Immunology/Innate Immunity
Infectious Diseases
Infectious Diseases/Bacterial Infections
Infectious Diseases/Neglected Tropical Diseases
Infectious Diseases/Tropical and Travel-Associated Diseases
Interleukin-1 Receptor-Like 1 Protein
Leptospirosis - complications
Leptospirosis - mortality
Leptospirosis - pathology
Male
Medical research
Middle Aged
Mortality
Receptors, Cell Surface - blood
Severity of Illness Index
Tropical diseases
title Soluble ST2 levels are associated with bleeding in patients with severe Leptospirosis
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