Infection/SepsisSerum lipid profile, cytokine production, and clinical outcome in patients with severe sepsis
Introduction
Despite our knowledge on the molecular biology of sepsis, attempts to improve the outcome of this syndrome and septic shock by modulating the inflammatory response have had limited success. This is, at least in part, a consequence of our limited understanding of the extremely complex mechanisms that regulate the inflammatory response.
Reviewing the literature, the ability of lipoproteins to bind and neutralize toxic bacterial substances has received more and more attention [1], [2]. In vitro as well as in vivo lipoproteins are shown to reduce the cytokine response and mortality rates in animal models of sepsis [3], [4]. Transgenic mice with elevated high-density lipoprotein (HDL) or low-density lipoprotein (LDL) concentrations are resistant to lipopolysaccharide (LPS) challenge. Infusion of a reconstituted HDL preparation reduced LPS-induced cytokine production in rabbits [5] and blocked many of the physiologic effects seen during endotoxemia in human volunteers [6].
Studies in septic patients or healthy volunteers injected with a low dose of endotoxin have shown that the systemic inflammatory response is associated with disruption of lipid metabolism [7], [8]. Low lipid concentrations are found in critically ill patients and patients with infections [9], [10]. Hypolipidemia may have important clinical consequences. Low lipid and lipoprotein concentrations were associated with a poor prognosis in few studies and correlated with the development of infectious disorders over a 15-year period [11], [12].
Previous evidence indicates that, during sepsis, cytokines such as interleukin (IL) 6 and tumor necrosis factor α (TNF-α) are significant regulators of lipoprotein metabolism [13], [14]. Most of these studies, so far, included only measurements upon admission of patients with no or limited follow-up [14], [15], [16]. In the present study, we sequentially measured total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C), and LDL cholesterol (LDL-C) levels as well as serum concentrations of TNF-α, IL-6, IL-8, IL-10, transforming growth factor (TGF) β1 in patients with severe sepsis for up to 10 days after admission. We also investigated the interrelationships between cytokines and lipid profile and, furthermore, the prognostic value of hypolipidemia for the final outcome.
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Patients
The study was performed at Patras University Hospital, a 700-bed tertiary referral hospital in Western Greece. A total of 64 patients (39 men and 25 women) with severe sepsis, admitted to the intermediate care unit of the department of medicine, were included during a period of 29 months. Fourteen patients were excluded from the study because of prior antibiotic use, incomplete sampling, or because they were lost to follow-up, leaving 50 patients (27 men, 23 women; mean age, 64.3 ± 6.8 years)
Characteristics of the study population
Patients who entered the study were 27 men (54%) and 23 women (46%). The number of patients with a particular diagnosis for origin of severe sepsis was as follows: pneumonia, 17; intra-abdominal infection, 16; urinary tract infection, 10; severe soft tissue infection, 4; osteomyelitis, 3. Microorganisms were isolated in 26 patients (gram-negative bacteria, 18; gram-positive bacteria, 8). The main patient's characteristics are shown in Table 1.
Of the 50 patients enrolled, 28 survived, whereas 22
Discussion
Lipoproteins have been implicated to play an important role in innate immunity. Profound changes in the concentration and composition of plasma lipids and lipoproteins have been described in critical illness [21], in intensive care patients with sepsis [22], and in cirrhotic patients with severe sepsis [23]. Previous few studies demonstrated that a marked decline in serum HDL levels has been documented [9], [15], [22], [23]. Our study extends these observations and demonstrates significantly
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