Effects of endotoxin on serum chemokines in man.
OBJECTIVE
Endotoxin is known to be a primary initiator of sepsis and septic shock. Migration of immunocompetent cells due to chemotactic attraction plays a central role in the initiation of the immune response. Two major groups of chemokines can be distinguished: C-x-C chemokines like Interleukin-8 attract mainly neutrophils, C-C chemokines (e.g. RANTES) attract monocytes and T-cells. The aim of this study was to get further insight into chemokine profiles after a single endotoxin bolus in man.


METHODS
We investigated the effect of systemically administered endotoxin (4ng/kg BW i.v.) in 8 healthy volunteers. Clinical data (heart rate, mean arterial pressure, temperature), serum levels of IL-8, and RANTES, as well as white blood cell count were obtained before and hourly for five hours after endotoxin administration.


RESULTS
Heart rate and MAP showed significant changes (p<0.05) after 2-3 hours. All volunteers presented with low-grade fever after 2 hours. WBC was elevated 43% and 63% after 4 and 5 hours, respectively. Both chemokines were significantly different from baseline two hours after endotoxin challenge: While IL-8 was significantly increased RANTES serum levels were diminished.


CONCLUSIONS
From our data we conclude that this endotoxin model was effective to mimic the clinical appearance of sepsis. Chemokines like IL-8 and RANTES are integrated in the early immune response to endotoxin challenge in man.
Schinkel
S
S
Department of Surgery, Evangelisches Krankenhaus, Witten, Germany. sschinkel@dwr.de
Schinkel
C
C
Pollard
V
V
Garofallo
R
R
Heberle
H
H
Reisner
P
P
Papaconstantinou
J
J
Herndon
D N
DN
D000328:Adult; D001794:Blood Pressure; D018946:Chemokine CCL5 / Q000097:blood*; D004731:Endotoxins / Q000008:administration & dosage*; D005260:Female; D006339:Heart Rate; D006801:Humans; D016209:Interleukin-8 / Q000097:blood*; D007958:Leukocyte Count; D008297:Male; D018805:Sepsis / Q000175:diagnosis
D018946:Chemokine CCL5; D004731:Endotoxins; D016209:Interleukin-8