The Effects of Combined Histamine and Platelet-activating Factor Antagonism on Systemic Anaphylaxis Induced by Immunoglobulin E in the Rabbit

Abstract

Of the mediators released during IgE-induced allergic reactions, it is not known which have the greatest physiologic import in systemic anaphylactic responses. This study describes the effects of histamine and platelet-activating factor (PAF) antagonism (combined) on IgE-induced systemic anaphylaxis in the rabbit. Pretreatment with 30 mumol/kg chlorpheniramine and 30 mumol/kg cimetidine with (Ch/Ci/WEB group) or without (Ch/Ci group) 2.2 mumol/kg of the PAF antagonist WEB 2086 inhibited the anaphylactic alterations in right ventricular pressure, total pulmonary resistance, and decrease in dynamic compliance but not systemic hypotension. Lethality was inhibited only in the Ch/Ci/WEB group. Because previous studies had shown WEB 2086 alone could inhibit the increase in pulmonary resistance, specificity studies were done to determine if WEB 2086 affected histamine activity or release. Responses to intravenously administered histamine (0.54 mumol/kg) were unaffected by WEB 2086 (13.1 mumol/kg). Also, WEB 2086 did not inhibit in vitro antigen-induced basophil degranulation. Thus, the decrease in dynamic compliance and pulmonary hypertension in IgE anaphylaxis appear to be mediated primarily by histamine and the increase in pulmonary resistance by histamine and/or PAF, whereas lethality appears to involve PAF. Some alterations, most notably systemic hypotension, likely involve other allergic mediators.