Background: Cimetidine preserves postoperative immune function and inhibits the growth of some cancers. In this study, the effect of cimetidine on the local immune response to colorectal carcinoma was investigated.
Methods: Forty-two patients scheduled for elective resection of colorectal carcinoma were randomized either to receive cimetidine for 1 week perioperatively or to act as controls. A lymphocyte density of 50 cells per high-power field (approximately 50% of the tumor/tissue interface) was considered a positive response. Patient survival was determined by Kaplan-Meier life table analysis. The effects of histamine and cimetidine on normal subject lymphocyte function was determined in a mitogen-stimulated proliferation assay.
Results: A positive lymphocyte response was observed in 5 of 24 control carcinoma patients (21%) and 10 of 18 cimetidine-treated carcinoma patients (56%) (P = 0.03). The presence of a lymphocyte response correlated with a better survival (P = 0.02). Histamine had an inhibitory effect on lymphocyte proliferation with a median effective dose of 5 x 10(-7) M. Cimetidine antagonized this effect with a negative logarithm of the cimetidine molar concentration required to reduce the effect of histamine in half of 6.55.
Conclusions: Histamine inhibits normal lymphocyte function, antagonized by cimetidine at a histamine type 2 receptor. Cimetidine increases lymphocyte infiltration of primary colorectal carcinoma, possibly by overcoming the immunosuppressive effects of high local histamine concentrations. The presence of a local lymphocyte response correlates with an improved 3-year survival.