Cimetidine and Granulopoiesis: Bone Marrow Culture Studies in Normal Man and Patients with Cimetidine-associated Neutropenia

Abstract

The effect of the H2-receptor antagonists, cimetidine and metiamide, [used to treat peptic ulcers] was studied on in vitro myeloid colony formation by bone marrow cells from 7 normal volunteers and 2 patients with a cimetidine-associated neutropenia. A cimetidine concentration of 500 .mu.g/ml produced 50% inhibition [I50] of normal granulocyte-macrophage colony formation, and 1000 .mu.g/ml of cimetidine completely suppressed proliferation. The inhibitory effect of metiamide occurred at lower concentrations: I50 at 250 .mu.g/ml and 95% inhibition at 350 .mu.g/ml. Cimetidine had a similar inhibitory effect on colony formation by recovery marrow from the 2 patients with cimetidine-associated neutropenia. Treatment of autologous and allogeneic marrows with patients'' acute phase sera and cimetidine showed no evidence of antibody-mediated suppression of granulopoiesis. At sufficiently high concentrations, cimetidine and metiamide apparently inhibit human bone marrow myeloid colony formation in vitro. H2-Receptor antagonists may produce neutropenia in a dose-related fashion by injury to granulocytic progenitor cells in vivo.