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G. Galatowicz, V. Chan, M. E. Stern, V. L. Calder; Effects of Brimonidine, Timolol, and Fixed Combination Brimonidine-Timolol on FcER1 Stimulated Human Mast Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2305.
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The IOP-lowering fixed combination of brimonidine/timolol has been reported to be associated with a lower rate of ocular allergy as compared with brimonidine alone. The aim of this study was to examine the effects of brimonidine, timolol or a combination on resting and FcεR1- activated human mast cells in vitro.
Human cord blood CD34+stem cells (CBMC; 105) were expanded in StemspanTM medium with SCF [100ng/mL], IL-6 [50ng/mL] and IL-3 [1ng/mL] during the first 14 days. At week 11, differentiation was confirmed by expression of CD117 (c-kit) and FcεR1. Unstimulated CBMC (106 cells/mL) were cultured either alone or in the presence of brimonidine [0.01 - 0.0001%], timolol [0.025 - 0.00025%] or a combination of both. For activation, CBMC were incubated with 4µg/ml IgE for 16 hr, with drug combinations given 30 min before adding 25µg/ml anti-IgE Ab. Culture supernatants were harvested at 1hr for histamine determination by ELISA. After 24 hr, cells were stained for intracellular expression of TNFα and IL-4, and analyzed by flow cytometry.
Histamine levels were low in unstimulated cells [9.9 ± 0.7 ng/mL] and were unaffected by the drugs. After FcεR1 stimulation, histamine levels were increased [36.6 ± 2.1 ng/mL; P<0.02] relative to control. Timolol decreased levels of histamine at the lowest concentration [0.00025%; P<0.03] whereas brimonidine increased histamine levels, although this failed to reach significance (P=0.052). The combination of drugs decreased histamine levels to those of controls. Under resting conditions, 100% CBMC were IL-4+ and less than 30% were TNFα+. Brimonidine, timolol and the combination of brimonidine and timolol had little or no effect on IL-4 or TNFα expression at 24 hr in resting or activated CBMC.
Resting CBMC were unaffected by the drugs. Timolol was selectively inhibitory for histamine secretion by stimulated CBMC. The brimonidine-mediated upregulation of histamine was reduced in the presence of timolol.
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