Histamine 2-receptor-mediated immunomodulation in the mouse. II. Immunomodulation by the H2 antagonist metiamide

Modulation of delayed hypersensitivity and antibody formation to sheep red cells by metiamide were studied in the mouse system. Depending on the time and dose of antigen and metiamide administration suppression or enhancement of the delayed hypersensitivity response was observed. The effects in this system did not differ from those reported for the H2 agonist tolazoline, which were most probably mediated by suppressor cells. As far as the humoral response was concerned metiamide tended to stimulate the IgM response. Optimal stimulation was reached if 50 mg metiamide/kg was administered 3 days before immunization with 2 x 10(8) SRBC. Under all conditions tested the IgG response was unaffected. These results suggest antagonistic effects of metiamide for tolazoline and adduce further evidence for the presence of H2 receptors on B cells. The IgM production per plasmacell was enhanced suggesting different H2 receptors to be involved in differentiative and proliferative B cell responses. The possible consequences of H2 antagonist application in human therapy are discussed.