Investigation of the potential use of immunosuppressive agent gliotoxin in organ transplantation.

Gliotoxin is an immunosuppressive secondary metabolite produced by several pathogenic fungi. It has previously been shown to prevent graft-versus-host disease in transplantation of allogeneic mouse bone marrow and to reduce the immunogenicity of human fetal pancreas. We here report on the effect of gliotoxin on the prevention of rejection of allografts in two distinct models. Bathing mouse thyroid tissue in gliotoxin solution for 16 hr prolonged graft survival following transplantation into allogeneic recipients. In contrast the perfusion of rat kidneys with gliotoxin followed by 1 hr of incubation before orthotopic transplantation had little success with preventing allograft rejection. This disparity is most likely due to the incubation in the renal model not allowing sufficient time for the elimination of antigen presenting cells in the donor organ. However, the success with the thyroid grafts demonstrates the potential of gliotoxin as an immunomodulating agent in organ transplantation and warrants further investigation in other systems.