Endotoxin increases plasma soluble tumor necrosis factor-related apoptosis-inducing ligand level mediated by the p38 mitogen-activated protein kinase signaling pathwayLub-de Hooge, M. N., de Jong, S., Vermot-Desroches, C., Tulleken, J. E., de Vries, E. G. E. & Zijlstra, J. G., 2004, In : Shock. 22, 2, p. 186 - 188 3 p.
Research output: Contribution to journal › Article › Academic › peer-review
Despite extensive knowledge about the mechanisms behind sepsis, this syndrome still caries a large morbidity and mortality rate. Dysregulated immune and coagulation systems are held responsible. However, additional pathophysiological mechanisms such as uncontrolled apoptosis induced by death receptor ligands might well play a role. P38 mitogen-activated protein (MAP) kinase inhibitors are considered as potential drugs in inflammatory diseases. Therefore, the effect of endotoxin administration on the response of soluble(s) tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL), a death receptor ligand, and the role of p38 MAP kinase inhibition was studied in 21 human volunteers. The volunteers received 30 min before the endotoxin infusion a single oral dose of placebo or the selective p38 MAP kinase inhibitor drug, RWJ-67657. Plasma sTRAIL increased 10-fold to 6564 +/- 511 pg/mL after 2.5 h. This increase was blocked completely by the highest dose of RW-J6765. This is the first report showing that endotoxin increases sTRAIL where the p38 MAP kinase signaling pathway is involved.
|Pages (from-to)||186 - 188|
|Number of pages||3|
|Publication status||Published - 2004|
- endotoxemia, sepsis, TRAIL, apoptosis, p38 MAPK, SEVERE SEPSIS, CYTOKINE PRODUCTION, SEPTIC SHOCK, MAP-KINASE, FAMILY, NEUTROPHILS, SUPPRESSION, INHIBITION, EXPRESSION, CHALLENGE