Safety evaluation for a cell-based immune support system in an ex vivo rat model of gram-negative sepsis.
Granulocyte dysfunction is a central component of immunodeficiency in septic patients. Granulocyte transfusions appear to be pathophysiologically useful; however, they cause unwanted side-effects in the lungs and other organs. This study evaluates the safety of an extracorporeal immune support system with granulocytic cells in a rat model of Gram-negative sepsis. Three groups of male CD rats received either saline (control group, I), a dose of Escherichia coli O7:K1 lethal to 90% of the animals (LD90) (septic group, II), or an LD90 dose of E. coli that was incubated with the human promyelocytic leukemia cell line (HL-60) (differentiated into the granulocytic direction) for 20 min prior to infusion (second septic group, III). The animals were observed for seven days. Pre-treatment with HL-60 cells resulted in no adverse effects in the group III animals. Significantly lower bacterial counts and endotoxin levels in the plasma were detected after 24 h as compared to group II (P < 0.05). Group III animals had better weight gain and more stable hemodynamics than group II animals (P < 0.01). Seven day survival was 0/8 in group II, 6/8 in group III, and 8/9 in group I (log-rank test: II-III: P < 0.001). The data suggest that extracorporeal use of granulocytes allows the therapeutic use of these cells while avoiding unwanted effects resulting from direct contact to internal organs.
Sauer
Martin
M
Department of Anesthesiology and Intensive Care Medicine, University of Rostock, Germany.
Altrichter
Jens
J
Kreutzer
Hans-Jürgen
HJ
Schmidt
Heidrun
H
Nöldge-Schomburg
Gabriele
G
Schmidt
Reinhard
R
Mitzner
Steffen R
SR
D000818:Animals; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000276:immunology / Q000628:therapy; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000628:therapy*; D006098:Granulocytes / Q000276:immunology / Q000637:transplantation*; D018922:HL-60 Cells; D006439:Hemodynamics; D006801:Humans; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D015996:Survival Rate