SUPPRESSIVE EFFECTS OF ANTIHISTAMINIC AND OR ANTI-PAF AGENTS ON PASSIVE ANAPHYLACTIC SHOCK IN MICE SENSITIZED WITH ALLOGENEIC MONOCLONAL IGE AND IGG(1) ANTIBODIES AND HYPERIMMUNE SERUM/

For the immunopharmacological characterization of murine passive anaph ylactic shock, the effects of antihistaminics and/or anti-platelet-act ivating factor (anti-PAF) agents were studied on the shock mediated by allogeneic monoclonal IgE and IgG(1) antibodies and hyperimmune serum . IgE antibody-mediated shock was strongly suppressed by cyproheptadin e (10 mg/kg, ip) in every strain regardless of the age and sex of the mice and the presence or absence of a shock potentiator. As far as tes ted with CTS, DS, and B6D2F1 mice, IgE antibody-mediated shock was als o suppressed by the other two antihistamines, triprolidine (10 mg/kg, ip) and oxatomide (100 mg/kg, po). This type of shock was not suppress ed by an anti-PAF agent, CV-6209 (3.3 mg/kg, iv), when tested on aged CTS mice given no shock potentiator and young DS mice given a potentia tor such as Bordetella pertussis organisms or DL-propranolol. IgG(1) a ntibody-mediated shock was also suppressed by cyproheptadine in genera l except for CTS mice. Suppression in the DL-propranolol-treated DS an d C3H/He mice was not very marked on sensitization with undiluted or s lightly diluted IgG1 ascites but quite striking on sensitization with properly diluted ascites. In contrast with the effect of cyproheptadin e, suppression by CV-6209 was obvious in aged CTS mice but not in youn g DL-propranolol-treated DS mice. The shock. in DL-propranolol-treated DS mice sensitized with undiluted or slightly diluted ascites was com pletely abolished by the combined use of these two agents. These resul ts suggest that histamine and/or PAF play a major role in IgE antibody - and IgG(1) antibody-mediated shock. However, so far as tested in you ng DS mice, the shock mediated by hyperimmune serum differed in drug s usceptibility from that mediated by the monoclonal antibodies. In the absence of shock. potentiators, prevention was produced by cyproheptad ine in the males which had been sensitized with the 1:4 or 1:8 dilutio n of the immune serum. In the presence of DL-propranolol, prevention w as not produced even by the combined treatment with cyproheptadine and CV-6209. Therefore, it is likely that some mediators other than hista mine and PAF, whose release is triggered by antibody isotypes other th an IgE and IgG(1), play a greater role for the shock mediated by hyper immune serum than for the shock mediated by IgE or IgG1 antibody, espe cially in the presence of shock potentiators.