On the pharmacology and toxicology of neutrophils.

OBJECTIVES

To study the effect of H1-antihistamines dithiaden (Dit) and loratadine (Lor) and compare it with that of histamine (His) on phorbolmyristate acetate (PMA) stimulated chemiluminescence (CL) of whole blood, isolated neutrophils, release of myeloperoxidase (MPO), and on superoxide (SO) generation.

METHODS

Luminol- and isoluminol-enhanced CL was applied for measuring the oxidative burst, spectrophotometry was used for determination of MPO (o-dianisidine) and SO generation (superoxide dismutase inhibition of cytochrome c).

RESULTS

Dit and Lor dose-dependently inhibited CL of whole blood and significantly decreased oxidative burst both at the extra- and intracellular sites of neutrophils. Release of MPO was decreased with both drugs tested in 10-times lower concentrations than was SO inhibition. Histamine (His) was much less effective in the inhibition of the parameters investigated.

CONCLUSIONS

Histaminergic drugs of the 1st generation inhibited oxidative burst of human phagocytes in whole blood and in isolated neutrophils. The rank order of potency to inhibit CL, MPO release and SO generation in PMA stimulated phagocytes was: Dit>Lor>His.