Extracorporeal cell therapy with granulocytes in a pig model of Gram-positive sepsis.
OBJECTIVE
Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. As granulocyte transfusions can trigger tissue injury via local effects of neutrophils, we hypothesized that extracorporeal treatment of plasma using granulocytes would prove beneficial while having less side effects.


METHODS
Prospective controlled three-armed animal study.


METHODS
Research laboratory.


METHODS
Twenty-one female immature pigs (7.5-12 kg, 7-9 weeks old).


METHODS
Three groups of spontaneously breathing, sedated pigs (n = 7 each) received an intravenous lethal dose of live Staphylococcus aureus over 1 hour. Although group I had no specific treatment (control), group II and III were subsequently treated for 4 hours with an extracorporeal device containing either no cells (sham control, group II) or human cell line-derived granulocytic cells (group III). Survival time and physiologic, biochemical, and hematologic parameters were monitored for 7 days.


RESULTS
All animals of group I died during the observation time (mean survival time: 70 hours). In group II, two of seven and in group III, six of seven animals survived the observation time (mean survival: 75 and 168 hours, respectively). Survival differences were significant between group I and III (p < 0.001) and between group II and III (p < 0.05) but not between group I and II (p = 0.43). Furthermore, group differences in bacterial blood concentrations, differential blood count, blood gases, lactate, and interleukins were observed. The extracorporeal cell treatment was well tolerated by the animals.


CONCLUSIONS
Extracorporeal therapy with granulocytic cells significantly improved survival in a pig model of sepsis. Further studies with this approach are encouraged.
Sauer
Martin
M
Department of Anesthesiology and Intensive Care Medicine, Medical Faculty of the University of Rostock, Rostock, Germany.
Altrichter
Jens
J
Kreutzer
Hans J
HJ
Lögters
Tim
T
Scholz
Martin
M
Nöldge-Schomburg
Gabriele
G
Schmidt
Reinhard
R
Mitzner
Steffen R
SR
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology / Q000628:therapy*; D006098:Granulocytes / Q000637:transplantation*; D018922:HL-60 Cells; D006801:Humans; D010956:Plasmapheresis / Q000379:methods; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*; D018805:Sepsis / Q000097:blood / Q000628:therapy*; D013211:Staphylococcus aureus / Q000302:isolation & purification; D016019:Survival Analysis; D013552:Swine