Attenuation of murine acute lethal graft-versus-host disease by the administration of DL-alpha-difluoromethylornithine.
Intravenous injection of 5 x 10(7) C57BL/6 (B6) lymphocytes into adult (C57BL/6 x DBA/2)F1 recipient mice results in acute lethal graft-versus-host (ALGVH) disease. This disorder is characterized by anemia, a diminished number of splenocytes, impaired cytotoxicity (CTX) against third party alloantigen, and impaired natural killer cell (NK) activity. Parental anti-F1 CTX is critical to the induction of ALGVH disease, and CTX in general has been reported to be dependent upon the presence of the low molecular weight polyamines essential for cell growth and differentiation. We now report that DL-alpha-difluoromethylornithine, a specific inhibitor of polyamine biosynthesis, attenuates the clinical expression of disease in mice undergoing ALGVH disease.
Singh
A B
AB
Division of Nephrology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.
Thomas
T J
TJ
Singh
M
M
Mann
R A
RA
D000740:Anemia / Q000209:etiology; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology*; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011073:Polyamines / Q000378:metabolism*; D013154:Spleen / Q000166:cytology
D011073:Polyamines; D000518:Eflornithine