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Safety evaluation for a cell-based immune support system in an ex vivo rat model of gram-negative sepsis.
- Source :
-
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy [Ther Apher Dial] 2009 Oct; Vol. 13 (5), pp. 444-50. - Publication Year :
- 2009
-
Abstract
- 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.
- Subjects :
- Animals
Disease Models, Animal
Escherichia coli Infections immunology
Escherichia coli Infections therapy
Gram-Negative Bacterial Infections immunology
Granulocytes immunology
HL-60 Cells
Hemodynamics
Humans
Male
Rats
Rats, Inbred Strains
Sepsis immunology
Sepsis microbiology
Survival Rate
Gram-Negative Bacterial Infections therapy
Granulocytes transplantation
Sepsis therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1744-9987
- Volume :
- 13
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 19788463
- Full Text :
- https://doi.org/10.1111/j.1744-9987.2009.00764.x