The effect of RP 59227, a platelet-activating factor antagonist, against antigen challenge and eosinophil and neutrophil chemotaxis in asthmatics

R. G. Townley, R. Eda, R. J. Hopp, Againdra K. Bewtra, M. S. Gillen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Study objectives: 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. Design: 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. Results: 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). Conclusions: 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.

Original languageEnglish
Pages (from-to)345-353
Number of pages9
JournalJournal of Lipid Mediators and Cell Signalling
Volume10
Issue number3
StatePublished - 1994

Fingerprint

Platelet Activating Factor
Chemotaxis
Eosinophils
Neutrophils
Antigens
Placebos
Pharmaceutical Preparations
Serum
Screening
Blood
Cross-Over Studies
RP 59227
Asthma
Safety

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Immunology

Cite this

The effect of RP 59227, a platelet-activating factor antagonist, against antigen challenge and eosinophil and neutrophil chemotaxis in asthmatics. / Townley, R. G.; Eda, R.; Hopp, R. J.; Bewtra, Againdra K.; Gillen, M. S.

In: Journal of Lipid Mediators and Cell Signalling, Vol. 10, No. 3, 1994, p. 345-353.

Research output: Contribution to journalArticle

@article{775c15f8c074406cb892d55ee6e3d3b8,
title = "The effect of RP 59227, a platelet-activating factor antagonist, against antigen challenge and eosinophil and neutrophil chemotaxis in asthmatics",
abstract = "Study objectives: 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. Design: 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. Results: 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). Conclusions: 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.",
author = "Townley, {R. G.} and R. Eda and Hopp, {R. J.} and Bewtra, {Againdra K.} and Gillen, {M. S.}",
year = "1994",
language = "English",
volume = "10",
pages = "345--353",
journal = "Prostaglandins and Other Lipid Mediators",
issn = "1098-8823",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - The effect of RP 59227, a platelet-activating factor antagonist, against antigen challenge and eosinophil and neutrophil chemotaxis in asthmatics

AU - Townley, R. G.

AU - Eda, R.

AU - Hopp, R. J.

AU - Bewtra, Againdra K.

AU - Gillen, M. S.

PY - 1994

Y1 - 1994

N2 - Study objectives: 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. Design: 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. Results: 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). Conclusions: 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.

AB - Study objectives: 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. Design: 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. Results: 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). Conclusions: 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.

UR - http://www.scopus.com/inward/record.url?scp=0028107020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028107020&partnerID=8YFLogxK

M3 - Article

VL - 10

SP - 345

EP - 353

JO - Prostaglandins and Other Lipid Mediators

JF - Prostaglandins and Other Lipid Mediators

SN - 1098-8823

IS - 3

ER -