In vitro investigations with the histamine H1 receptor antagonist, epinastine (WAL 801 CL), on isolated human allergic effector cells.
OBJECTIVE
Skin mast cells, basophils and eosinophils are effector cells of acute and subacute allergic responses due to their capacity to produce a large number of (pro)inflammatory mediators. Histamine H1 receptor antagonists, such as epinastine (WAL 801 CL), have been described to partially exert antiallergic and antiinflammatory effects both in vivo and in vitro in addition to their antihistaminergic properties. The aim of the present study was to investigate whether epinastine could influence the in vitro activation of isolated human skin mast cells, basophils and eosinophils induced by different secretagogues.


METHODS
Cells were isolated from healthy women following plastic surgery and healthy blood donors, respectively. Mast cells were isolated by enzymatic digestion of the skin. Blood cells were isolated by gradient centrifugation and negative selection with magnetic beads.


RESULTS
A wide range of concentrations of the drug (1 nmol/l to 100 micromol/l) did not significantly inhibit histamine release from basophils induced by immunologic (anti-IgE, concanavalin A, priming factors interleukin-3 and interleukin-5) and non immunologic (A23187, ionomycin, 12-o-tetradecanoyl-phorbol-13-acetate, C5a, formyl-methionyl-leucyl-phenylalanine) stimuli. Furthermore, the drug had no effect on A23187-induced release of eosinophil cationic protein from eosinophils. However, at a concentration >0.1 nmol/l, IgE-mediated LTC4 production from basophils was significantly suppressed. Histamine release from skin mast cells due to anti-IgE or A23187 was inhibited by epinastine in a dose-dependent fashion, whereas substance P-induced activation as well as stem cell factor priming were not. Epinastine did not inhibit isolated protein kinase C from rat brain.


CONCLUSIONS
The results confirm previous in vivo and in vitro observations obtained from animal models that epinastine exerts antiallergic and antiinflammatory effects. Whether the observed effects are due to non specific membrane interactions or by influencing intracellular signal transduction elements has to be further elucidated.
Amon
U
U
PsoriSol Centre for Dermatology and Allergy, Hersbruck, Germany. amon@psorisol.de
Gibbs
B F
BF
Buss
G
G
Nitschke
M
M
D001491:Basophils / Q000187:drug effects / Q000201:enzymology; D002469:Cell Separation; D003984:Dibenzazepines / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D007093:Imidazoles / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012867:Skin / Q000166:cytology / Q000201:enzymology
D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D011493:Protein Kinase C; C053090:epinastine