Interferon-gamma prevents graft-versus-host disease after allogeneic bone marrow transplantation in mice.
Lethally irradiated C3H/Law mice were injected (i.v.) with C57BL/Rij allogeneic bone marrow cells to induce a delayed type graft-vs-host disease (GVHD). Signs of GVHD first became apparent in the third week after transplantation. The disease resulted in a mortality rate of 70% at 80 days. Treatment with IFN-gamma twice weekly, for a period of 6 wk, starting at the time of bone marrow transplantation (BMT), completely prevented overt GVHD, as evidenced by a lack of diarrhea and no mortality during the follow-up period of 100 days after BMT. Also, the histologic GVHD lesions in the gastrointestinal tract were almost completely abrogated by the IFN-gamma treatment. All long term survivors were proven to be chimeras. During the induction phase of GVHD, the number of Con A-induced, IFN-gamma-producing cells in the spleen was significantly reduced in the IFN-gamma-treated mice as compared with control mice. These results suggest that the normally enhanced production of endogenous IFN-gamma in the spleen at the time of hematopoietic reconstitution after BMT is down-regulated by exogenously administered IFN-gamma. This cytokine-mediated strategy to prevent GVHD might be an alternative to the current strategy of in vitro depletion of T cells for allogeneic BMT.
Brok
H P
HP
Department of Pediatrics, University Hospital Leiden, The Netherlands.
Heidt
P J
PJ
van der Meide
P H
PH
Zurcher
C
C
Vossen
J M
JM
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003967:Diarrhea / Q000517:prevention & control; D004064:Digestive System / Q000473:pathology; D005260:Female; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D014184:Transplantation, Homologous
D007371:Interferon-gamma