Colchicine allows prolonged survival of highly reactive renal allograft in the rat

Colchicine, with its immunosuppressive properties, has been used with beneficial effects in autoimmune diseases. Whether colchicine, by virtue of the above properties, could attenuate the process of kidney allograft rejection in the rat is investigated in this report. Untreated Lewis rats (N = 6) given an incompatible kidney allograft from Brown-Norway rats rejected the graft within 12 days. Colchicine at a daily ip dose of 40 (N = 6) or 10 (N= 4) μg/kg promoted long-term survival (>170 days) of major histocompatibility complex-incompatible kidney grafts. Animals (N = 4) given 4 μg of colchicine per kilogram had a graft failure within 10 days. Experiments have also been performed to evaluate the effect of colchicine withdrawal at different time intervals from transplantation on subsequent allograft survival. Colchicine (40 μg/kg per day ip) was given for 12, 6, or 1 mo or for 15 days to an additional four groups of six animals each without any other immunosuppressants. The withdrawal of colchicine did confer long-term inhibition of the immune system in animals treated for at least 1 mo, as documented by a graft survival of more than 80 days. By contrast, those animals who discontinued colchicine after only 15 days of treatment had graft rejection within the next 8 days. Mixed lymphocyte culture experiments showed a significant (P <0.01) reduction of the proliferation of peripheral blood lymphocytes taken from all groups of animals 30 days after colchicine withdrawal when challenged with Brown-Norway lymphocytes. These findings confirm the immunomodulatory effect of colchicine observed in previous studies and show for the first time that such a property could be used to prevent allograft rejection, at least in the rat.