Examination of the immunosuppressive effect of Delta(9)-tetrahydrocannabinol in streptozotocin-induced autoimmune diabetes

Delta (9)-Tetrahydrocannabinol (Delta (9)-THC) is capable of modulating a v ariety of immune responses, but has not been evaluated in models of immune- based diabetes. The objectives of the present study were: (a) to investigat e the affect of Delta (9)-THC in an established model of multiple low dose streptozotocin (MLDSTZ)-induced autoimmune diabetes: and (b) to determine t he contribution of the immune response in the MLDSTZ model. CD-1 mice were treated with 40 mg/kg STZ for 5 days in the presence or absence of Delta (9 )-THC treatment. Delta (9)-THC administered orally in corn oil at 150 mg/kg for Il days attenuated, in a transient manner, the MLDSTZ-induced elevatio n in serum glucose and loss of pancreatic insulin. MLDSTZ-induced insulitis and increases in IFN-gamma, TNF alpha and IL-12 mRNA expression were all r educed on Day 11 by co-administration of Delta (9)-THC. In separate studies , six doses of Delta (9)-THC, given after completion of STZ treatment, was found equally effective in attenuating mice from MLDSTZ-induced diabetes. S tudies performed using B6C3F1 mice showed moderate hyperglycemia and a sign ificant reduction in pancreatic insulin by MLDSTZ in the absence of insulit is. In addition, MLDSTZ produced a less pronounced hyperglycemia compared t o CD-1 mice that was not attenuated by Delta (9)-THC. These results suggest that MLDSTZ can initiate direct p-cell damager thereby augmenting the dest ruction of p-cells by the immune system. Moreover, these results indicate t hat Delta (9)-THC is capable of attenuating the severity of the autoimmune response in this experimental model of autoimmune diabetes. (C) 2001 Elsevi er Science B.V. All rights reserved.