Effect of a PAF antagonist, BN52063, on antigen-induced, acute, and late-onset cutaneous responses in atopic subjects.
Platelet-activating factor (PAF) is a potent phospholipid that has been implicated as a mediator of allergic inflammatory responses, since it may induce a biphasic response and eosinophil infiltration in the skin that is reminiscent of antigen-induced reactions after cutaneous administration in man. We have studied the effect of a PAF antagonist, the ginkgolide mixture, BN52063, to determine the role of PAF in antigen-induced cutaneous responses in a double-blind, placebo-controlled, crossover study in 10 atopic subjects. Two hours after ingestion of BN52063 (120 mg), the wheal-and-flare response to intradermal PAF (200 ng), but not to histamine (1 micrograms), was inhibited, as previously described in nonatopic subjects. The late-onset component of the response to allergen (8 hours after injection) was significantly attenuated from 2.89 +/- 0.76 cm3 to 1.41 +/- 0.58 cm3 (p less than 0.05). Although the early wheal response was reduced in 50% of subjects, it was not significant overall, nor was there any significant reduction in the flare response. These observations suggest that PAF contributes to the late inflammatory response to allergen that is known to be associated with an inflammatory cell (predominantly eosinophil) infiltrate. This lends support to the idea that PAF is a mediator of allergic inflammation and that PAF antagonists may have a therapeutic role in allergic diseases.
Roberts
N M
NM
Department of Pharmacology, King's College, London University, England.
Page
C P
CP
Chung
K F
KF
Barnes
P J
PJ
D000208:Acute Disease; D000328:Adult; D000941:Antigens / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology*; D005260:Female; D006632:Histamine / Q000276:immunology; D006801:Humans; D007783:Lactones; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology
D000941:Antigens; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; C050422:BN 52063; D006632:Histamine