Changes in bronchial anaphylactic reactivity induced in guinea-pigs by long-term treatment with histamine H2-agents.

Guinea-pigs were sensitized to ovalbumin (OA) by immunization regimens chosen to cause antigen-induced bronchial anaphylactic responses mediated mainly either by IgE-like antibodies or by IgG1-like antibodies. Treatment of the IgE-producing animals for three weeks with the histamine H2-receptor antagonist cimetidine (1 mg kg-1 i.p. once a day) or with the H2-agonist dimaprit (0.1, 1.0, or 10 mg kg-1 i.p. once a day) led to a significantly reduced bronchial response capacity compared with that of the saline-treated controls challenged intravenously with antigen one week after the end of treatment. The changes were biphasic and not strictly dose-dependent. In contrast, acute treatment of immunized animals with a single dose of cimetidine (10 or 30 mg kg-1 i.v.) or dimaprit (1 or 10 mg kg-1 i.v.) 2 min before challenge with OA did not significantly affect the bronchial anaphylactic response. However, long-term treatment with cimetidine (10 mg kg-1) or the dimaprit analogue, S-[4-(N, N-dimethylamino)-butyl] isothiourea (SKF Compound 91488) (1 mg kg-1), which is reported not to activate H2-receptors, had no effect on the response capacity. Treatment with cimetidine (1 mg kg-1) or dimaprit (1 mg kg-1) did not influence the response capacity to antigen challenge in IgG1- type animals. Dimaprit (1 mg kg-1) did not affect the responsiveness to intravenous provocation with histamine in 'IgE-type' animals. Antigen-induced release of histamine from chopped lung tissue in vitro was not significantly affected in 'IgE-type' animals treated with cimetidine (1 mg kg-1) or dimaprit (1 mg kg-1). Treatment of immunized animals with cimetidine or dimaprit one week before and one week after a booster injection of antigen also led to reduced response capacity compared with that of saline-treated controls. However, the serum levels of IgE-like homocytotropic antibodies of these animals were not reduced; on the contrary, those of IgG1-antibody were increased in dimaprit-treated animals. These data show that intermittent treatment with histamine H2-agents reduces reagin-mediated anaphylactic response capacity in vivo in actively sensitized guinea-pigs by an as yet undefined mode of action.