Protective Effect of Curcumin in an F¹-Hybrid Model of Acute Graft-vs.-Host Disease.

Curcumin (diferuloylmethane), a pigment from the rhizomes of Curcuma Longa, has anti-oxidant, anti-tumor and anti-inflammatory properties. It has been shown that curcumin can inhibit the development of experimental allergic encephalomyelitis, a Th1-mediated, autoimmune, demyelinating disease that affects the central nervous system in mice. Because acute GVHD involves the development of a Th1-mediated immune response, and is characterized by the development of a potent, systemic, inflammatory response, we wished to determine whether curcumin might also protect mice from developing acute GVHD in the C57BL/6→(C57BL/6 x DBA/2)F¹-hybrid model. We found that ip injections of curcumin (100 micrograms dissolved in 25 microliters of DMSO), given once a day, every 2 days, protected recipients from developing acute, lethal GVHD. Two thirds of the treated group survived well past day 100 post-transplantation. Control GVH mice treated with DMSO alone became moribund within three weeks of transplantation, the time at which mice with acute GVHD typically succumb. To ensure that the protective effects of curcumin were not due to abortion of the graft, we analyzed T cell engraftment in some of the long-term survivors. In the surviving mice tested on days 135 and 275 post-transplantation, we were unable to detect any cells of recipient origin in the spleen. Furthermore, the percentage of donor-derived CD4⁺ cells ranged from 32–47% and the percentage of CD8⁺ T cells ranged from 25–42% in the non-adherent spleen cell fraction. Data from these experiments suggest that curcumin can protect mice from developing acute, lethal GVHD.