A Focus on SepsisLevels of oxidized low-density lipoproteins are increased in patients with severe sepsis☆
Introduction
Sepsis is defined as a clinical syndrome including infection and the systemic inflammatory response [1], [2]. Sepsis emerges to severe sepsis when one or more organ dysfunctions reemerge. Individual factors (eg, genetic factors or premorbid health status), extent of infection, and complicating organ dysfunction have a substantial impact on the disease process, host response, and mortality. Several inflammatory and procoagulant markers have been identified indicating this response as well as the disease severity in severe septic patients (eg, procalcitonin [PCT], interleukin 6 [IL-6], d-dimer) [1], [2], [3].
Free radical generation represents one of many proinflammatory reactions produced along the cytokine cascade in a septic organism [4]. Oxidative stress mediated by reactive oxygen intermediates (ROIs) leads to oxidation of DNA, proteins, and lipids of the endothelium [5]. It has been demonstrated that plasma redox status—mostly measured by levels of lipoperoxides or myeloperoxidase—relates to the severity of the disease in critically ill patients [6], [7], [8].
Moreover, oxidation of low-density lipoproteins (LDLs) has been shown to occur in diseases associated with acute or chronic infection and inflammation [9], [10] as well as in arteriosclerosis [11], [12], [13], [14]. Several mediators and enzymes have been identified to initiate LDL oxidation (eg, metal ions, lipoxygenase, thiols, superoxides, myeloperoxidase, or inducible nitric oxide synthase) [8]. Drotrecogin α (activated) has been demonstrated to reduce mortality in patients with severe sepsis within the recombinant human activated protein C worldwide evaluation in severe sepsis trial [15]. However, the time course of ox-LDL levels in severe sepsis as well as its possible modulation by the treatment with drotrecogin α (activated) has not been evaluated yet.
It was hypothesized that the inflammatory response of patients with severe sepsis may result in changes of plasma levels of ox-LDL and that drotrecogin α (activated) might influence ox-LDL levels.
Therefore, the aim of the present study was to investigate the time course of ox-LDL levels in septic patients treated with or without drotrecogin α (activated).
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Study population
A total of 68 patients having severe sepsis were prospectively enrolled for this study from March 2001 until October 2003. Respectively, 31 patients were treated with drotrecogin α (activated) and constituted the treatment group. The remaining 37 patients not treated with drotrecogin α (activated) were defined as controls. The study was performed at the Department of Medicine at the University Hospital Mannheim, Germany, and at the Department of Anesthesiology at the University Hospital Bonn,
Results
Baseline characteristics of 68 patients having severe sepsis are given in Table 1. Age of patients treated with drotrecogin α (activated) (n = 31, treatment group) was 55 years compared to a mean age of 63 years of patients not treated with drotrecogin α (activated) (n = 37, control group) (P = .02). The most common primary site of infection in both groups was the lung (n = 14; n = 21), followed by intraabdominal infections (n = 9; n = 10). The mean APACHE II score of patients treated with
Discussion
The present study evaluated levels of ox-LDL in 68 patients during the first week of severe sepsis. The ox-LDL levels increase significantly during the first 7 days of severe sepsis. Moreover, no treatment effect of drotrecogin α (activated) was observed on ox-LDL concentrations in the time course of patients having severe sepsis.
This study demonstrates for the first time that ox-LDL levels increase in patients having severe sepsis. These findings contribute to a better understanding of the
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2014, Journal of Lipid ResearchCitation Excerpt :After rinsing with wash buffer, 100 μl of enzyme conjugate was added to each well and incubated for 1 h at room temperature. After subsequent washing, 3,3‘,5,5‘-tetramethylbenzidine substrate was added and the developed color was measured using an ELISA reader (BioTek Instruments, Inc., USA) at a wavelength of 450 nm (28). Standard curve was prepared for each assay run using calibrators and control supplied along with the assay kit.
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This work was supported by a grant of the Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.