Histamine type-2 receptor antagonist immune modulation. I. Increased cell-mediated cytotoxicity in normal and in down-regulated systems.

Cimetidine, a histamine type-2 receptor antagonist, is capable of immunoregulating T cell-mediated proliferative responses in both man and mouse. We present data that show that cell-mediated cytotoxicity (CMC) is also increased by cimetidine in normal and down-regulated murine splenocytes. Timed addition and removal of cimetidine from CMC generation cultures localizes the cimetidine effect to the first 24 hours of the alloantigen sensitization process. Cimetidine partially reverses CMC suppression by suppressor cells generated in vitro in a dose response manner; the result depends on the number of suppressor cells added. Mixed tumor lymphocyte cytotoxicity of splenocytes from syngeneic-tumor-bearing mice is increased by in vivo cimetidine treatment, which results in prolongation of concomitant tumor immunity. These data support the concept that cimetidine may have potential as a clinical immunofacilitator in down-regulated states of immunity.