Cimetidine protection against lethal tumor challenge in mice.

Cimetidine, a histamine type-2 receptor antagonist, has been shown to augment proliferative responses of lymphocytes in man and mouse and to increase in vitro-generated murine cell-mediated cytotoxicity. It has been suggested by others that histamine receptors are involved in modulating the immune response through mediation of suppressor cell function. We have previously described a murine tumor model in which suppressor function increases with advancing tumor burden. We now have examined the in vivo effect of cimetidine on survival in this tumor-bearing murine model. Cimetidine was administered in the drinking water to C57BL/6 mice after an intraperitoneal injection of an LD90 dose of EL4 tumor cells. The survival rate was noticeably improved (56%) with an optimal dose of cimetidine (100 mg/kg/day) after 30 days, compared to that of water-treated control mice (10%). This protective effect was present with young (2 months old) as well as older (8 months old) mice. Rechallenge of cimetidine-treated survivors with a six times LD100 tumor dose and continuation of cimetidine produced a 33% survival rate. Comparison of cimetidine (100 mg/kg/day) with different doses of diphenhydramine (histamine type-1 antagonist) showed the protective effect to be more type-2 specific. The mechanism of action of cimetidine remains unclear, but based on this work and work by others, we think that cimetidine probably modulates suppressor cell function. Cimetidine may have potential as an immunomodulator.