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 dyn amics 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 H-3-receptor blocker with partial H-1- and H-2-agonism) on the dynamics of the cutaneous hypersensitivity rea ction. The skin blister technique was used to collect inflammatory cel ls after intradermal (i.d.) administration of grass pollen antigen, hi stamine and betahistine to 11 atopic volunteers. In this open, cross-o ver study, volunteers were randomly allocated to five treatment protoc ols i.e. (a) histamine 1 mu g i.d.; (b) betahistine 57,114 and 285 mu g i.d.; (c) i.d. grass pollen antigen; (d) (c) plus oral betahistine; (e) (c) plus oral betahistine, cetirizine, (H-1-blocker) and cimetidin e (H-2-blocker). Blister fluid containing cells were collected on micr oscope slides at 6 and 24 h after i.d. injections. The areas of the wh eal 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 si gnificantly 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. Intra dermal betahistine induced significantly more neutrophil and eosinophi l vacuolization than histamine and, in contrast to the latter, also me diated a concentration-dependent late phase induration. The results of this study suggest that the H-3-receptor regulates a feedback system in conjunction with that previously proven for the H-2-receptor. Conse quenly H-2- and H-3-blockade control the release of different mediator s.