Topical ophthalmic β blockers may cause release of histamine through cytotoxic effects on inflammatory cells

Aim - To evaluate the effects of β blockers used in ophthalmology on the release of histamine from mixed cell preparations containing human leucocytes and basophils. Methods - A mixed leucocyte and basophil preparation was obtained from venous blood of healthy non-atopic volunteers. Cell preparations were then incubated with betaxolol, metipranolol, timolol, or carteolol. After incubation for 1 hour the histamine content of the supernatant was analysed by automated fluorometric analysis. Cell viability was tested by measuring lactate dehydrogenase (LDH) concentrations. Results - Betaxolol and metipranolol in concentrations between 10-2 M and 10-3 M liberated histamine from human blood cells in a dose dependent manner. Carteolol and timolol had no effect on histamine at these concentrations. At the same concentrations LDH was also detected in the supernatants of cell suspensions incubated with metipranolol or betaxolol. Conclusions - Betaxolol and metipranolol induce substantial histamine release from human leucocytes, probably as a result of their cytotoxic effect.