Sepsis after severe injury interrupts caspase-dependent processing of interleukin-18.
BACKGROUND
Cysteine proteases (caspases) participate in the activation process of interleukin-18 (IL-18), a key cytokine for septic organ failure. This study evaluates the influence of caspase blockade on secretion of IL-18 into whole blood in patients with multiple injuries and in patients with severe sepsis.


METHODS
Heparinized blood was collected from patients with multiple injuries, from septic patients, as well as from healthy humans. Whole blood was stimulated for 24 hours with lipopolysaccharide (LPS) or Staphylococcus aureus in the presence or absence of the caspase inhibitors Z-VAD and Z-DEVD. IL-18 was measured by enzyme-linked immunosorbent assay.


RESULTS
S. aureus Cowan strain differentially increased the release of IL-18 in the three study populations, whereas LPS was ineffective. Z-VAD and to a lesser degree Z-DEVD decreased (p < 0.05) S. aureus Cowan strain I-induced secretion of IL-18 into whole blood from control subjects and trauma patients. Caspase inhibitors did not influence release of IL-18 into whole blood from septic patients.


CONCLUSIONS
Secretion of IL-18 into whole blood from healthy humans and trauma patients can be effectively controlled through blockade of caspase activity. In contrast, during sepsis, alternative mechanisms may regulate secretion of IL-18.
Oberholzer
A
A
Division of Trauma Surgery, University Hospital Zurich, Switzerland.
Feilner
A
A
Hentze
H
H
Steckholzer
U
U
Kurimoto
M
M
Trentz
O
O
Ertel
W
W
D018806:APACHE; D000328:Adult; D016022:Case-Control Studies; D061945:Caspase Inhibitors; D020169:Caspases / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009104:Multiple Trauma / Q000276:immunology*; D018805:Sepsis / Q000097:blood / Q000276:immunology*
D061945:Caspase Inhibitors; D020382:Interleukin-18; D020169:Caspases