Inhibition of suppressor cell function by cimetidine in a murine model

Immunomodulatory effects of cimetidine, an H₂ histamine receptor antagonist, have been reported in humans and animals. To define these effects more clearly, the action of cimetidine on suppressor cell function was studied utilizing a murine model of contact hypersensitivity. Intravenous inoculation of BALB c mice with DNP-coupled syngeneic spleen cells induced the production of DNP-specific suppressor cells which could easily be demonstrated by a reduction in ear swelling after contact sensitization with 1-fluoro-2,4-dinitrobenzene (DNFB) following transfer of spleen and lymph node cells to naive syngeneic recipients. Cimetidine treatment of animals in which suppressor cells were induced resulted in an inability of these mice to transfer cellular suppression as measured by development of a normal immunologic response in the recipient mice. The effect of cimetidine was both dose and time related. While all groups receiving cimetidine showed some loss of suppressor cell function, the maximum effect (up to 100% inhibition) was seen when 50 mg/kg of cimetidine was administered intraperitoneally 2 days before or on the day of suppressor cell induction. Some restoration also occurred when cimetidine was given after the day of induction. It has been shown that suppressor cells possess histamine receptors which may be involved in suppressor cell activation. The results indicate that cimetidine may inhibit the functioning of these receptors.