Phagocytic cell function in recurrent endotoxemia in sheep.
Sepsis syndrome in severely traumatized patients is supposedly due to a blockade of the phagocytic cell system--for example, the reticulo endothelial system (RES) and polymorph nuclear leukocytes (PMNL), which cause insufficient elimination of bacterial substances (e.g., endotoxin). In contrast we found in a previous study using a model of acute endotoxemia that RES clearance is enhanced, while PMNL function gave evidence for decompensation. In order to clarify whether or not our results were just a matter of single dose endotoxemia, we have investigated RES and PMNL function in a sheep model with recurrent endotoxemia. A sheep receiving endotoxin at a dose of 1 microgram/kg body weight every 12 hours was monitored over a 5-day period. RES clearance was calculated by the half-life of Tc99 phytate each day. The PMNL function was determined by measuring chemiluminescence (CL) of isolated PMNL and total blood. The half-life of Tc99 phytate decreased from 56 min to 44 min with endotoxin (P less than or equal to 0.01) the second day and further to 42 min (P less than or equal to 0.002) on the third day. Values then returned to baseline until the end of study. Zymosan induced and luminol enhanced CL response indicated an acute cellular exhaustion after the first endotoxin dose. Under subsequent endotoxin administration, a daily attenuation of the acute response was noted in combination with baseline opsonin capacity. Our results give evidence that also in recurrent endotoxemia RES function is characterized by a sufficient clearance, whereas the PMNL function remains decreased and therefore possibly is responsible for the well-known clinical post-traumatic septic complications.
Seekamp
A
A
Unfallchirurgische Klinik, Medizinische Hochschule Hannover, Federal Republic of Germany.
Dwenger
A
A
Weidner
M
M
Regel
G
G
Sturm
J A
JA
D000818:Animals; D004731:Endotoxins / Q000008:administration & dosage; D006207:Half-Life; D006439:Hemodynamics; D008163:Luminescent Measurements; D008165:Luminol; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D018805:Sepsis / Q000503:physiopathology*; D012756:Sheep; D013667:Technetium / Q000378:metabolism; D015054:Zymosan
D004731:Endotoxins; D008165:Luminol; D013667:Technetium; D015054:Zymosan