title: Plasma ceramide and lysophosphatidylcholine inversely correlate with mortality in sepsis patients.
abstract: Recent data indicate that ceramide (Cer) and lysophosphatidylcholine (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 Cer and LPC by quantitative tandem mass spectrometry in 102 sepsis patients starting with the day at which the sepsis criteria were fulfilled for the first time, as well as on day 4 and day 11. The values were compared with 56 healthy controls and correlated with sepsis-related mortality within 30 days of study entry. Most Cer 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 Cer-SPM ratios were increased, whereas LPC-PC ratios were decreased in sepsis patients. The increased Cer-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 the first ex vivo indication for the role of Cer and lysophospholipids in systemic inflammation in humans.
authors.affiliation: Institute for Clinical Chemistry, University of Regensburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Drobnik
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.forename: Franz-Xaver
authors.initials: FX
authors.lastname: Audebert
authors.forename: Dieter
authors.initials: D
authors.lastname: Frohlich
authors.forename: Thomas
authors.initials: T
authors.lastname: Gluck
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.forename: Gregor
authors.initials: G
authors.lastname: Rothe
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood*; D005260:Female; D006801:Humans; D008244:Lysophosphatidylcholines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000097:blood; D018805:Sepsis / Q000097:blood* / Q000209:etiology / Q000401:mortality*; D013109:Sphingomyelins / Q000097:blood; D016019:Survival Analysis
chemical_list: D002518:Ceramides; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D013109:Sphingomyelins