ISSN:
1432-1041
Keywords:
Schistosomiasis
;
Histamine1+2+3-antagonists
;
cellular dynamics
;
cutaneous hypersensitivity reaction
;
cimetidine
;
cetirizine
;
betahistine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary The biphasic cutaneous hypersensitivity response elicited by intradermal administration of S. haematobium antigen to patients with schistosomiasis may be used as a model for drug effects on cell dynamics. As the effects of H1- and H2-blockade, and the possible involvement of H3-receptors, have not been elucidated, we have examined the effects of combinations of cetirizine, cimetidine and betahistine on the response of patients with confirmed schistosomiasis. The skin blister technique was used. After intradermal administration of antigen, blister fluid containing inflammatory cells was collected on microscope slides at 6 and 24 h, and a differential cell count was done; and the area of induration was measured at 0.25, 1, 6 and 24 h. These baseline tests were repeated after 3 days of pretreatment with cetirizine 20 mg/d, after the addition of cimetidine 1200 mg/d for 3 further days, and finally after adding on betahistine 32 mg/d for 3 days. Simultaneous H1- and H2-blockade with cetirizine plus cimetidine caused a significantly greater reduction in induration than cetirizine (H1-blockade) alone; the reductions from the baseline value were 70%, 78%, 89%, 97%, and 33%, 53%, 43%, 30%, at times 0.25, 1, 6 and 24 h, respectively. The triple combination with the addition of betahistine (H1- and H2-agonist and H3-antagonist) resulted in reductions of 37%, 63%, 95% and 97% at the same times. The most striking changes in cellular dynamics were a significant increase in eosinophil (6 h) and neutrophil (6 h) vacuolation, and enhancement of monocyte (24 h) and basophil (6 h) accumulation, when the betahistine was added. Simultaneous H1 and H2-blockade significantly reduced eosinophil accumulation and vacuolation from baseline, and it also significantly inhibited progressive activation of neutrophils and eosinophils from 6 to 24 h when compared to baseline. As cell vacuolation and migration were increased when induration was minimal, we suggest that vascular effects were inhibited by H1- and H2-blockade, while other receptors, e.g. H3, regulated certain cellular effects. As histamine is known to cause immune modulation via H1- and H2-receptors, it is possible that the H3-receptor influences cell activity by a feedback mechanism, or perhaps by the release of other cytokines.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00315545
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