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Papers In Press, published online ahead of print January 16, 2003
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Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg 93042
Corresponding Author: gerd.schmitz{at}klinik.uni-regensburg.de
Recent data indicate that ceramide and lysophsophatidylcholine (LPC) regulate immune cell functions. Since these bioactive lipids are generated in blood plasma by inflammatory lipases we hypothesized that they may be involved in the process of acute systemic sepsis. In order to provide support for this hypothesis we analyzed the plasma levels of ceramide and LPC by quantitative tandem mass spectrometry in 102 sepsis patients starting with the day at which sepsis criteria were fulfilled for the first time as well as on day 4 and day 11. The values were compared to 56 healthy controls and correlated with sepsis related mortality within 30 days after study entry. Most ceramide species were increased in sepsis patients, while all LPC species were markedly decreased. In addition, we determined the molar ratios with their precursor molecules sphingomyelin (SPM) and phosphatidylcholine (PC) which reflect the enzymatic reactions responsible for their formation. Species specific as well as total ceramide/SPM ratios were increased, whereas LPC/PC ratios were decreased in sepsis patients. The increased ceramide/SPM ratios as well as the decreased LPC/PC ratios showed a strong predictive power for sepsis related mortality. Together with existing data from in vitro experiments and animal models the results provide first ex vivo indication for a role of ceramide and lysophospholipids in systemic inflammation in humans.
Revised on January 3, 2003
Accepted on January 6, 2003
Plasma ceramide and lysophosphatidylcholine inversely correlate with mortality in sepsis patients
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