Townley R G, Eda R, Hopp R J, Bewtra A K, Gillen M S
Allergic Disease Center, Creighton University, Omaha, NE 68178.
J Lipid Mediat Cell Signal. 1994 Sep;10(3):345-53.
Platelet-activating factor (PAF), an inflammatory mediator, induces microvascular leak, eosinophil chemotaxis, and possibly increases non-specific bronchial hyperresponsiveness in humans. PAF antagonists may have clinical benefits in asthma.
We determined the safety and efficacy of a 240 mg oral dose of RP-59227 in attenuating the early and late phase antigen challenge in eight asthmatics, using a double-blind, placebo-controlled, crossover design. Also determined was the effect of the ex vivo addition of PAF following placebo or drug and the level of neutrophil (NCA) and eosinophil chemotactic activity (ECA) in the serum immediately, and 4 h after antigen challenge with either drug or placebo.
There was not a significant difference in the maximum percent fall in FEV1 during the early and late phase on screening or placebo days or drug RP-59227 days. There was a significant inhibitory effect (p < 0.05) in peak ECA and NCA in blood after RP-59227. The addition of PAF to ex vivo serum was less effective in inducing chemotaxis to eosinophils following RP-59227 (p < 0.05).
RP-59227 attenuated the release of NCA and ECA after antigen challenge, and reduced the effect of exogenously added PAF in inducing eosinophil chemotaxis but did not protect against the antigen-induced early or late phase response.
血小板活化因子（PAF）是一种炎症介质，可引起微血管渗漏、嗜酸性粒细胞趋化，并可能增加人类非特异性支气管高反应性。PAF拮抗剂可能对哮喘具有临床益处。
我们采用双盲、安慰剂对照、交叉设计，确定了240mg口服剂量的RP-59227对8名哮喘患者减轻抗原激发早期和晚期反应的安全性和有效性。还测定了在给予安慰剂或药物后体外添加PAF的效果，以及在给予药物或安慰剂进行抗原激发后即刻和4小时时血清中嗜中性粒细胞（NCA）和嗜酸性粒细胞趋化活性（ECA）的水平。
在筛查日、安慰剂日或服用RP-59227药物日期间，早期和晚期FEV1最大下降百分比无显著差异。服用RP-59227后，血液中峰值ECA和NCA有显著抑制作用（p<0.05）。在RP-59227处理后的体外血清中添加PAF诱导嗜酸性粒细胞趋化的效果较差（p<0.05）。
RP-59227可减轻抗原激发后NCA和ECA的释放，并降低外源性添加PAF诱导嗜酸性粒细胞趋化的作用，但不能预防抗原诱导的早期或晚期反应。
