Improved survival following induction of GVHD following lipopolysaccharide immunization.
OBJECTIVE
Graft-vs-host disease (GVHD) is still the primary limitation to the wider application of allogeneic bone marrow transplantation (BMT). On the one hand, it predisposes transplant recipients to risk of bacterial, fungal, and viral infections, on the other, lipopolysaccharide (LPS), an endotoxin found in the cell walls of gram-negative bacteria, has been shown to play a significant role in the development and severity of GVHD following allogeneic myeloablative BMT. Our study focused on immunization of recipient and donor mice with endotoxin prior to transplantation, in an attempt to reduce mortality caused by gram-negative bacterial infections posttransplantation.


METHODS
In one experiment, recipient mice were immunized with LPS prior to BMT, whereas in another experiment, donor mice were immunized prior to BMT. The mice were evaluated for development of GVHD and for survival.


RESULTS
Our results showed that injection of low-dose LPS to mice prior to induction of GVHD with allogeneic spleen cells saved more than 40% of the recipients, whereas all mice in the untreated control group died. The survival of recipients of spleen cells from immunized donors rose to 54% and clinical signs of GVHD were attenuated as compared to control mice inoculated with spleen cells obtained from unimmunized donors.


CONCLUSIONS
This immunization protocol suggests that immunization of the donor or the recipient against LPS prior to transplantation may be protective against gram-negative bacteria.
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, Hadassah University Hospital, Jerusalem, Israel.
Ali
A
Abdul-Hai
Lola
L
Weiss
Shimon
S
Slavin
Reuven
R
Or
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D006086:Graft vs Host Disease / Q000150:complications / Q000276:immunology; D016905:Gram-Negative Bacterial Infections / Q000209:etiology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014611:Vaccination / Q000379:methods
D008070:Lipopolysaccharides