Attenuation of murine graft-versus-host reactivity by azathioprine

Journal Article · Tue Jul 01 04:00:00 EDT 1980 · Transplantation; (United States)

DOI:https://doi.org/10.1097/00007890-198007000-00012· OSTI ID:5578874

Shand, F L

The therapeutic effects of azathioprine were evaluated in a murine graft-versus-host (GVH) model. A single high dose (200 mg/kg) of azathioprine, administered to FI recipients 2 to 3 days after the injection of parental spleen cells, abrogated the ensuing GVH reaction. Lower doses of the drug, even when injected over an extended period of time (14 days), were found to be ineffective. However, high doses of azathioprine failed to protect when FI recipients were sublethally irradiated or injected with cyclophosphamide before GVH induction, and even the transfer of syngeneic FI spleen cells immediately after irradiation failed to alter this outcome. Further analysis of the changes that occurred in sublethally irradiated recipients revealed that the protective effect of azathioprine on CBA leads to (CBA x C57BL)FI GVH reaction was totally abrogated by doses of irradiation as low as 200 rad. Further experiments in which death was used as an indicator of GVH disease showed that lethality could not be reversed in sublethally irradiated FI recipients by the transfer of syngeneic FI spleen cells unless approximately 10 days were allowed to elapse between syngeneic reconstitution and GVH induction. Since syngeneic FI cells from spleen, lymph node, or bone marrow all behaved similarly, it seems likely that the increased severity of GVH reaction induced by prior immunosuppression may not be attributable to a simple cell deletion event.

• Research Organization: The Wellcome Research Labs. Beckenham, England
• OSTI ID: 5578874
• Journal Information: Transplantation; (United States), Journal Name: Transplantation; (United States) Vol. 30:1; ISSN TRPLA
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALI METAL ISOTOPES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BODY
BONE MARROW
CESIUM ISOTOPES
DRUGS
GRAFT-HOST REACTION
HEMATOPOIETIC SYSTEM
IMMUNOSUPPRESSION
IRRADIATION
ISOTOPES
LYMPH NODES
LYMPHATIC SYSTEM
MAMMALS
MICE
ORGANS
RADIOSENSITIVITY EFFECTS
RODENTS
SOMATIC CELLS
SPLEEN CELLS
SUBLETHAL IRRADIATION
TIME DEPENDENCE
TISSUES
VERTEBRATES