Suppressive effects of antihistaminic and/or anti-PAF agents on passive anaphylactic shock in mice sensitized with allogeneic monoclonal IgE and IgG1 antibodies and hyperimmune serum.
For the immunopharmacological characterization of murine passive anaphylactic shock, the effects of antihistaminics and/or anti-platelet-activating factor (anti-PAF) agents were studied on the shock mediated by allogeneic monoclonal IgE and IgG1 antibodies and hyperimmune serum. IgE antibody-mediated shock was strongly suppressed by cyproheptadine (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 tested with CTS, DS, and B6D2F1 mice, IgE antibody-mediated shock was also suppressed by the other two antihistamines, triprolidine (10 mg/kg, ip) and oxatomide (100 mg/kg, po). This type of shock was not suppressed 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 potentiator such as Bordetella pertussis organisms or DL-propranolol. IgG1 antibody-mediated shock was also suppressed by cyproheptadine in general except for CTS mice. Suppression in the DL-propranolol-treated DS and C3H/He mice was not very marked on sensitization with undiluted or slightly diluted IgG1 ascites but quite striking on sensitization with properly diluted ascites. In contrast with the effect of cyproheptadine, suppression by CV-6209 was obvious in aged CTS mice but not in young DL-propranolol-treated DS mice. The shock in DL-propranolol-treated DS mice sensitized with undiluted or slightly diluted ascites was completely abolished by the combined use of these two agents. These results suggest that histamine and/or PAF play a major role in IgE antibody- and IgG1 antibody-mediated shock. However, so far as tested in young DS mice, the shock mediated by hyperimmune serum differed in drug susceptibility from that mediated by the monoclonal antibodies. In the absence of shock potentiators, prevention was produced by cyproheptadine in the males which had been sensitized with the 1:4 or 1:8 dilution of the immune serum. In the presence of DL-propranolol, prevention was not produced even by the combined treatment with cyproheptadine and CV-6209. Therefore, it is likely that some mediators other than histamine and PAF, whose release is triggered by antibody isotypes other than IgE and IgG1, play a greater role for the shock mediated by hyperimmune serum than for the shock mediated by IgE or IgG1 antibody, especially in the presence of shock potentiators.
Kimura
S
S
Developmental Research Laboratories, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
Watanabe
A
A
Takeuchi
M
M
Nagata
M
M
Harada
M
M
D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002417:Cattle; D003533:Cyproheptadine / Q000494:pharmacology; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007518:Isoantibodies / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010879:Piperazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011433:Propranolol / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000276:immunology; D014311:Triprolidine / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D006634:Histamine H1 Antagonists; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D010879:Piperazines; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; D012710:Serum Albumin, Bovine; D014311:Triprolidine; D003533:Cyproheptadine; D007073:Immunoglobulin E; D011433:Propranolol; C015408:oxatomide