Role of the Monocyte Differentiation Antigen CD14 and Lipopolysaccharide-Binding Protein (LBP) in the Recognition of Endotoxin and Gram-Negative Bacteria: In vitro Function, Animal Models and Therapeutic Implications

1 Cytokines may parallel or regulate the beneficial effects of beta-adrenoceptor antagonist treatment observed in chronic heart failure (CHF) patients. Therefore, this study was performed in order to investigate alterations of cytokine levels in beta-blocker-treated patients suffering from CHF. 2 We investigated plasma cytokine levels in eight healthy controls and 12 CHF patients. The patients were treated with standard medication (CHFstd) or with standard medication and additional beta1-blocker metoprolol (CHFmet). Interleukin-(IL)-1alpha, IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF), soluble TNF receptor type 1 (sTNF-R1), sTNF-R2, and sCD14 were measured by ELISA. 3 IL-1alpha and IL-1beta were not detectable in any of the tested groups. IL-2, TNF, or sCD14 were not altered as compared with healthy control subjects. CHFstd patients expressed enhanced IL-1ra, IL-6, IL-8, IL-10, sTNF-R1 and sTNF-R2. In CHFmet patients IL-1ra, IL-6 and IL-8 remained at the same level. In contrast, sTNF-R1 levels were significantly reduced, although not to control, whereas the sTNF-R2 and IL-10 were reduced to control levels. 4 The cAMP levels of mononuclear cells--recalculated for the patients included in this study from previous work [Werner et al. (2001). Basic Res. Cardiol., 96, 290]--correlated inversely with the sTNF-R2 data (Pearson, r = -0.46; P = 0.041; Spearman, r = -0.64, P = 0.002). 5 The present data indicate an interaction of the neurohumoral and the cytokine system in CHF patients at the cAMP level. Thus, measurement and correlation of sTNF-R2 and cAMP may provide a tool useful during investigation of beta-blocker therapy.

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Elevated Levels of Lipopolysaccharide-Binding Protein and Soluble CD14 in Plasma in Neonatal Early-Onset Sepsis

Berner

Fürll

Stelter

et al. 2002

Clin Vaccine Immunol

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No data on lipopolysaccharide-binding protein (LBP) in newborns with sepsis have been available up to now. We therefore determined levels of LBP and soluble CD14 (sCD14) in plasma of healthy and septic neonates in order to evaluate their potential diagnostic role. The study included prospectively collected patient samples of two recently published studies on cytokine expression in neonatal sepsis. Twenty-nine septic patients were enrolled in the present analysis. Samples-either cord blood or peripheral blood-from patients admitted within the first 24 h of life for suspicion of sepsis and cord blood samples of a control group of 40 healthy mature infants delivered spontaneously were analyzed. For seven patients of the septic group, a second sample collected between 24 and 48 h of life was available. Levels of sCD14 and LBP in plasma were determined by an enzyme immunoassay using recombinant CD14 and LBP as standards. LBP and sCD14 were correlated to cytokine plasma levels. In septic neonates, LBP (median, 36.6 versus 7.8 g/ml; P < 0.001) and sCD14 (median, 0.42 versus 0.28 g/ml; P < 0.001) levels were highly elevated when compared to those of healthy neonates and strongly correlated to granulocyte colony-stimulating factor (G-CSF), interleukin-1␤ (IL-1␤), IL-6, and IL-8 levels. LBP levels in septic neonates analyzed between 24 and 48 h of life even increased when compared to samples obtained at or shortly after delivery (median, 36.6 versus 60 g/ml; P ‫؍‬ 0.038). In summary, levels of LBP in plasma of neonates with early-onset sepsis are significantly elevated; the elevated plasma levels seem to persist for more than 24 h, which could provide the clinician with a prolonged time period to identify the newborn with bacterial sepsis.

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Role of the Monocyte Differentiation Antigen CD14 and Lipopolysaccharide-Binding Protein (LBP) in the Recognition of Endotoxin and Gram-Negative Bacteria: In vitro Function, Animal Models and Therapeutic Implications

Cited by 3 publications

References 105 publications

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Stereoselective metabolic disruption of cypermethrin by remolding gut homeostasis in rat

The enhanced plasma levels of soluble tumor necrosis factor receptors (sTNF‐R1; sTNF‐R2) and interleukin‐10 (IL‐10) in patients suffering from chronic heart failure are reversed in patients treated with β‐adrenoceptor antagonist

Elevated Levels of Lipopolysaccharide-Binding Protein and Soluble CD14 in Plasma in Neonatal Early-Onset Sepsis

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