TY - JOUR
T1 - Initial posttraumatic translocation of NF-κB and TNF-α mRNA expression in peripheral blood monocytes of trauma patients with multiple injuries
T2 - A pilot study
AU - Biberthaler, Peter
AU - Stegmaier, Julia
AU - Mayer, Verena
AU - Kirchhoff, Chlodwig
AU - Neth, Peter
AU - Mussack, Thomas
AU - Mutschler, Wolf
AU - Jochum, Marianne
PY - 2004/12
Y1 - 2004/12
N2 - Post-traumatic inflammation is connected to monocyte dysfunction characterized by reduced NF-κB translocation during the first post-traumatic days. Because the exact dynamic of monocytic NF-κB translocation in patients directly after trauma remains unclear, the aim of this pilot study was to measure the intranuclear presence of NF-κB in monocytes from patients with multiple injuries initially after the trauma and during the early post-traumatic period and to compare these results with downstream-placed mRNA expression alteration of TNF-α, as well as with clinical data. Eleven patients were enrolled with an Injury Severity Score of 16 to 66 points, and blood samples were drawn on admission within 90 min and at 6, 12, 24, 48, and 72 h after trauma. NF-κB translocation of monocytic nuclear protein was analyzed by electrophoretic mobility shift assay and was quantified by densitometry as arbitrary units. In addition, monocytes of healthy volunteers were analyzed either native (-, control) or after LPS stimulation (+, control). For determination of downstream mRNA encoding for TNF-α, quantitative reverse transcriptase-PCR was performed. For both parameters, the negative control values were set as baseline (=1) and results from positive controls and patients were given as a relative alteration ratio without unit. Initial post-traumatic NF-κB translocation was significantly increased in trauma patients on admission (88 ± 37) and 6 h after trauma (59 ± 28) compared with the baseline level. In contrast, TNF-α mRNA was not increased on admission (1.7 ± 0.9) and decreased even below baseline after 12 h. The substantial information of our study arises from the analysis of the dynamic of NF-κB translocation of monocytes. Enabled by closely matched sequential blood sampling strictly standardized to the traumatic event, an essential increase of monocytic signal transduction and transcription could be elucidated in the very early post-traumatic period, which precedes the down-regulation of the innate immune system.
AB - Post-traumatic inflammation is connected to monocyte dysfunction characterized by reduced NF-κB translocation during the first post-traumatic days. Because the exact dynamic of monocytic NF-κB translocation in patients directly after trauma remains unclear, the aim of this pilot study was to measure the intranuclear presence of NF-κB in monocytes from patients with multiple injuries initially after the trauma and during the early post-traumatic period and to compare these results with downstream-placed mRNA expression alteration of TNF-α, as well as with clinical data. Eleven patients were enrolled with an Injury Severity Score of 16 to 66 points, and blood samples were drawn on admission within 90 min and at 6, 12, 24, 48, and 72 h after trauma. NF-κB translocation of monocytic nuclear protein was analyzed by electrophoretic mobility shift assay and was quantified by densitometry as arbitrary units. In addition, monocytes of healthy volunteers were analyzed either native (-, control) or after LPS stimulation (+, control). For determination of downstream mRNA encoding for TNF-α, quantitative reverse transcriptase-PCR was performed. For both parameters, the negative control values were set as baseline (=1) and results from positive controls and patients were given as a relative alteration ratio without unit. Initial post-traumatic NF-κB translocation was significantly increased in trauma patients on admission (88 ± 37) and 6 h after trauma (59 ± 28) compared with the baseline level. In contrast, TNF-α mRNA was not increased on admission (1.7 ± 0.9) and decreased even below baseline after 12 h. The substantial information of our study arises from the analysis of the dynamic of NF-κB translocation of monocytes. Enabled by closely matched sequential blood sampling strictly standardized to the traumatic event, an essential increase of monocytic signal transduction and transcription could be elucidated in the very early post-traumatic period, which precedes the down-regulation of the innate immune system.
KW - EMSA
KW - Immune system
KW - Multiple injury
KW - Multiple organ failure
KW - NF-κB
KW - Nuclear protein
KW - Posttraumatic
KW - Response
UR - http://www.scopus.com/inward/record.url?scp=9644262625&partnerID=8YFLogxK
U2 - 10.1097/01.shk.0000142819.68823.14
DO - 10.1097/01.shk.0000142819.68823.14
M3 - Article
C2 - 15545823
AN - SCOPUS:9644262625
SN - 1073-2322
VL - 22
SP - 527
EP - 532
JO - Shock
JF - Shock
IS - 6
ER -