Glucocorticosteroids inhibit leukotriene production

Background: The mode of action of corticosteroids, important drugs in the treatment of inflammatory disease, is not yet fully understood. Corticosteroids are known to inhibit phospholipase A₂ in unprimed eosinophils and basophils, preventing leukotriene synthesis, but their effect on cells that are already primed is unknown. Objective: As inflammatory cells from atopic subjects are often primed in vivo, we studied the effects of two potent corticosteroids on basophil sulfidoleukotriene production in peripheral blood mixed leukocytes (PBML) from in-season and out-of-season atopic individuals. Methods: Cells were incubated for 24 hours with mometasone furoate or beclomethasone dipropionate, primed with IL-3, stimulated with calcium ionophore, buffer, allergen or anti-IgE, and leukotriene production was quantified. Results: Peripheral blood mononuclear leukocytes from five of ten donors (in season) produced elevated sulfidoleukotrienes without a stimulus; cells from seven donors responded to anti-IgE by increased sulfidoleukotrienes. Neither steroid consistently affected sulfidoleukotriene production in anti-IgE-stimulated cells which were releasing sulfidoleukotrienes in the absence of a stimulant. In comparison, sulfidoleukotriene production was significantly reduced by 0.01 to 10 nM beclomethasone dipropionate or mometasone furoate when the cells were primed with IL-3 after exposure to the drug and stimulated with calcium ionophore or allergen, but no dose-relationship was apparent. Leukotriene production by PBML in response to anti-IgE was potently inhibited by all concentrations of mometasone furoate (0.01 nM to I μM) with an inhibitory concentrations₅₀ of less than 0.01 nM. Beclomethasone dipropionate inhibited sulfidoleukotriene production in this group (inhibitory concentration₅₀ 6 nM) in a dose-dependent manner. Conclusions: Sulfidoleukotriene production and, conceivably, priming may be more effectively inhibited by mometasone furoate than beclomethasone dipropionate.