Kimura S, Watanabe A, Nagata M, Niinomi Y, Harada M
Developmental Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Immunol Invest. 1996 Sep-Nov;25(5-6):425-34. doi: 10.3109/08820139609055732.
To determine the main mediators for mouse anaphylactic shock, the suppression of active anaphylactic shock by cyproheptadine, an antagonist of histamine/serotonin, and CV-6209, an antagonist of platelet-activating factor (PAF), was systematically evaluated using various mouse strains. The suppression was quite heterogeneic depending on the mouse strain and method for sensitization. When sensitization was done with bovine serum albumin (BSA) plus Bordetella pertussis organisms, anaphylactic shock in C57BL/6N mice was suppressed by cyproheptadine but not by CV-6209. In contrast, shock in C3H/HeN and WBB6F1-W/Wv mice was suppressed by CV-6209 but not by cyproheptadine. Shock in BALB/c mice was suppressed by both agents but that in WBB6F1-(+)/+ mice was not at all by either one. DS and BDF1 mice showed differences due to the length of the sensitization period; shock was not suppressed by cyproheptadine with a shorter sensitization (9 to 11 days) but clearly suppressed with prolonged sensitization of 14 to 15 days. Shock in DS, WBB6F1-(+)/+ and BDF1 mice, which was not suppressed by either agent alone, was strongly suppressed by the combination of the two agents. In animals which had been sensitized with BSA emulsified with Freund's complete adjuvant (FCA) and given DL-propranolol as a shock potentiator, a similar pattern of drug susceptibility as that in the pertussis-vaccinated animals was obtained in general, although a discrepancy was seen with regard to the suppression of CV-6209 in C3H/HeN and BDF1 mice. Synergistic suppression by CV-6209 and cyproheptadine was also very clear with the WBB6F1-(+)/+ mice sensitized using FCA. In addition, results quite similar to those with cyproheptadine were obtained with the other two antihistamines, triprolidine almost devoid of antiserotonin activity and oxatomide, in testing with BDF1 mice sensitized using Bordetella pertussis organisms. From these findings, the conclusion is that histamine and PAF play major roles solely or in combination in mouse active anaphylactic shock.
为确定小鼠过敏性休克的主要介质，使用多种小鼠品系系统评估了组胺/5-羟色胺拮抗剂赛庚啶和血小板活化因子（PAF）拮抗剂CV-6209对活性过敏性休克的抑制作用。根据小鼠品系和致敏方法的不同，这种抑制作用存在很大差异。当用牛血清白蛋白（BSA）加百日咳杆菌进行致敏时，赛庚啶可抑制C57BL/6N小鼠的过敏性休克，但CV-6209不能。相反，CV-6209可抑制C3H/HeN和WBB6F1-W/Wv小鼠的休克，但赛庚啶不能。BALB/c小鼠的休克可被两种药物抑制，但WBB6F1-(+)/+小鼠的休克则完全不受任何一种药物抑制。DS和BDF1小鼠因致敏期长短而表现出差异；致敏期较短（9至11天）时，赛庚啶不能抑制休克，但致敏期延长至14至15天时则可明显抑制。DS、WBB6F1-(+)/+和BDF1小鼠的休克单独使用任何一种药物均不能抑制，但两种药物联合使用则可强烈抑制。在用弗氏完全佐剂（FCA）乳化的BSA致敏并给予DL-普萘洛尔作为休克增强剂的动物中，尽管在C3H/HeN和BDF1小鼠中CV-6209的抑制作用存在差异，但总体上获得了与接种百日咳疫苗动物相似的药物敏感性模式。对于使用FCA致敏的WBB6F1-(+)/+小鼠，CV-6209和赛庚啶的协同抑制作用也非常明显。此外，在用百日咳杆菌致敏的BDF1小鼠进行测试时，另外两种几乎没有抗5-羟色胺活性的抗组胺药曲普利啶和奥沙米特，得到了与赛庚啶非常相似的结果。从这些发现得出的结论是，组胺和PAF单独或联合在小鼠活性过敏性休克中起主要作用。
