Ceramide concentrations in septic patients: a possible marker of multiple organ dysfunction syndrome.
OBJECTIVE
To investigate the concentrations of mononuclear cell-associated ceramide and serum tumor necrosis factor-alpha (TNF-alpha) in patients with sepsis and to assess their predictive value for the development of multiple organ dysfunction syndrome (MODS).


METHODS
Prospective, cohort study.


METHODS
Intensive care unit and two research laboratories at a university hospital.


METHODS
Twenty-three adult patients admitted to an intensive care unit meeting the criteria for diagnosis of sepsis.


METHODS
Blood samples were collected at the time when diagnosis of sepsis was made.


RESULTS
Mononuclear cell-associated ceramide and serum TNF-alpha were significantly elevated in the samples from the septic patients compared with the control individuals (318.01+/-270.15 pmol/10(6) cells vs. 99.90+/-52.75 pmol/10(6) cells; p<.001, and 28.52+/-18.77 pg/mL vs. 10.43+/-3.37 pg/mL; p<.0001, respectively), and a direct correlation linked ceramide and TNF-alpha concentrations (r2 = .90, p<.00001). In the septic patients who went on to develop MODS, ceramide and TNF-alpha were significantly higher compared with the no MODS patients (489.22+/-264.93 pmol/10(6) cells vs. 131.23+/-99.02 pmol/10(6) cells; p<.0001, and 40.96+/-18 pg/mL vs. 14.95+/-5.60 pg/mL; p<.001, respectively). The receiver operating characteristic curves demonstrated that both TNF-alpha and ceramide were prognostic of MODS, but ceramide concentrations were more efficient predictors.


CONCLUSIONS
These observations suggest that mononuclear cells of peripheral blood from patients with sepsis are committed to undergo apoptosis, because there is evidence that ceramide acts as an endogenous mediator of apoptosis. The strong correlation we found between cell-associated ceramide and serum TNF-alpha supports the hypothesis that this cytokine plays an important role in activating the sphingomyelin pathway and ceramide generation in patients with sepsis. In addition, this study provides evidence that consistent concentrations of mononuclear cell-associated ceramide may predict progression toward MODS in septic patients.
Delogu
G
G
Institute of Anesthesia and Intensive Care, La Sapienza University, Rome, Italy.
Famularo
G
G
Amati
F
F
Signore
L
L
Antonucci
A
A
Trinchieri
V
V
Di Marzio
L
L
Cifone
M G
MG
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D002518:Ceramides / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D002518:Ceramides; D014409:Tumor Necrosis Factor-alpha