The influence of betahistine on the dynamics of the cutaneous hypersensitivity reaction in patients with grass pollen allergy.
Histamine has been well documented as an immune modulator, but the dynamics of a number of histamine receptor agonists and antagonists have not been similarly established. The aim of this study was to determine the effect of betahistine (an H3-receptor blocker with partial H1- and H2-agonism) on the dynamics of the cutaneous hypersensitivity reaction. The skin blister technique was used to collect inflammatory cells after intradermal (i.d.) administration of grass pollen antigen, histamine and betahistine to 11 atopic volunteers. In this open, cross-over study, volunteers were randomly allocated to five treatment protocols i.e. (a) histamine 1 microgram i.d.; (b) betahistine 57, 114 and 285 micrograms i.d.; (c) i.d. grass pollen antigen; (d) (c) plus oral betahistine; (e) (c) plus oral betahistine, cetirizine, (H1-blocker) and cimetidine (H2-blocker). Blister fluid containing cells were collected on microscope slides at 6 and 24 h after i.d. injections. The areas of the wheal and flare and of induration were measured, respectively, at 0.25, and, 1, 6 and 24 h. Combined oral therapy with cetirizine, cimetidine and betahistine reduced the area of grass pollen-induced induration significantly at all time periods, but caused a significant increase in eosinophil and neutrophil vacuolisation during the late phase reaction. This did not occur with orally administered betahistine alone. Intradermal betahistine induced significantly more neutrophil and eosinophil vacuolization than histamine and, in contrast to the latter, also mediated a concentration-dependent late phase induration. The results of this study suggest that the H3-receptor regulates a feedback system in conjunction with that previously proven for the H2-receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Snyman
J R
JR
Department of Pharmacology University of Pretoria, South Africa.
Sommers
D K
DK
van Wyk
M
M
Gregorowski
M D
MD
D000328:Adult; D001621:Betahistine; D018592:Cross-Over Studies; D017449:Dermatitis, Allergic Contact / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D017442:Histamine Agonists / Q000008:administration & dosage; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000175:diagnosis / Q000473:pathology; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000473:pathology; D007428:Intradermal Tests; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D006109:Poaceae / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000150:complications*
D017442:Histamine Agonists; D001621:Betahistine