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.