Immune restoration and/or augmentation of local xenogeneic graft versus host reaction by Cimetidine in vitro

Abstract

The immunorestorative effect of Cimetidine in vitro on the T cell-induced local GVH reaction in vivo was studied in 43 cancer patients and 43 normal healthy donors. Both low dose (10(-5) M) and high dose (10(-4) M) Cimetidine induced significant, albeit partial, immune restoration among GVHR-negative cancer patients (p less than 0.05, p less than 0.01, respectively) with the high dose being significantly more effective (p less than 0.05). In contrast, similar Cimetidine doses induced only moderate augmentation (p greater than 0.05) among GVHR-positive cancer patients and a marginal one among normal healthy donors. In the latter 2 groups, Cimetidine was found to be occasionally detrimental in that it induced a conversion from a positive to a negative GVH reaction. These results support the concept of anti-suppressor cell activity ascribed to Cimetidine. However, the possibility of a detrimental effect should be born in mind in planning future clinical trials. We propose that the use of Cimetidine be limited to cancer patients with documented increase in suppressor cell activity associated with defective T cell function under close serial monitoring.