Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia

The effects of steroids on the outcome of sepsis are dose dependent. Low doses appear to be beneficial, but high doses do not improve outcome for reasons that are insufficiently understood. The effects of steroids on systemic inflammation as a function of dose have not previously been studied in hum...

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Vydané v:Journal of Immunology Ročník 178; číslo 3; s. 1845 - 1851
Hlavní autori: de Kruif, Martijn D, Lemaire, Lucienne C, Giebelen, Ida A, van Zoelen, Marieke A D, Pater, Jennie M, van den Pangaart, Petra S, Groot, Angelique P, de Vos, Alex F, Elliott, Peter J, Meijers, Joost C M, Levi, Marcel, van der Poll, Tom
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.02.2007
Predmet:
Adult
Biomarkers - blood
Blood Coagulation - drug effects
Chemokines - blood
Cytokines - blood
Cytokines - drug effects
Dose-Response Relationship, Drug
Endothelial Cells - drug effects
Endotoxemia - drug therapy
Endotoxemia - pathology
Escherichia coli
Fibrinolysis - drug effects
Humans
Inflammation - drug therapy
Lipopolysaccharides - administration & dosage
Male
Neutrophil Activation - drug effects
Prednisolone - administration & dosage
Prednisolone - pharmacology
ISSN:0022-1767, 1365-2567
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Shrnutí:The effects of steroids on the outcome of sepsis are dose dependent. Low doses appear to be beneficial, but high doses do not improve outcome for reasons that are insufficiently understood. The effects of steroids on systemic inflammation as a function of dose have not previously been studied in humans. To determine the effects of increasing doses of prednisolone on inflammation and coagulation in humans exposed to LPS, 32 healthy males received prednisolone orally at doses of 0, 3, 10, or 30 mg (n = 8 per group) at 2 h before i.v. injection of Escherichia coli LPS (4 ng/kg). Prednisolone dose-dependently inhibited the LPS-induced release of cytokines (TNF-alpha and IL-6) and chemokines (IL-8 and MCP-1), while enhancing the release of the anti-inflammatory cytokine IL-10. Prednisolone attenuated neutrophil activation (plasma elastase levels) and endothelial cell activation (von Willebrand factor). Most remarkably, prednisolone did not inhibit LPS-induced coagulation activation, measured by plasma concentrations of thrombin-antithrombin complexes, prothrombin fragment F1+2, and soluble tissue factor. In addition, activation of the fibrinolytic pathway (tissue-type plasminogen activator and plasmin-alpha(2)-antiplasmin complexes) was dose-dependently enhanced by prednisolone. These data indicate that prednisolone dose-dependently and differentially influences the systemic activation of different host response pathways during human endotoxemia.
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ISSN:0022-1767
1365-2567
DOI:10.4049/jimmunol.178.3.1845