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.
Department of Anesthesiology and Intensive Care Medicine, University of Rostock, Germany.
Martin
M
Sauer
Jens
J
Altrichter
Hans-Jürgen
HJ
Kreutzer
Heidrun
H
Schmidt
Gabriele
G
Nöldge-Schomburg
Reinhard
R
Schmidt
Steffen R
SR
Mitzner
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