GLUCOCORTICOSTEROIDS INHIBIT LEUKOTRIENE PRODUCTION

Background: The mode of action of corticosteroids, important drugs in the treatment of inflammatory disease, is not yet fully understood. Co rticosteroids are known to inhibit phospholipase A(2) in unprimed eosi nophils and basophils, preventing leukotriene synthesis, but their eff ect on cells that are already primed is unknown. Objective: As inflamm atory cells from atopic subjects are often primed in vivo, we studied the effects of two potent corticosteroids on basophil sulfidoleukotrie ne production in peripheral blood mixed leukocytes (PBML) from in-seas on 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: Perip heral 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. N either steroid consistently affected sulfidoleukotriene production in anti-IgE-stimulated cells which were releasing sulfidoleukotrienes in the absence of a stimulant. In comparison, sulfidoleukotriene producti on was significantly reduced by 0.01 to 10 nM beclomethasone dipropion ate or mometasone furoate when the cells were primed with IL-3 after e xposure 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 1 mu M) with an inhibitory concentra tion,, of less than 0.01 nM. Beclomethasone dipropionate inhibited sul fidoleukotriene production in this group (inhibitory concentration(50) 6 nM) in a dose-dependent manner. Conclusions: Sulfidoleukotriene pro duction and, conceivably, priming may be more effectively inhibited by mometasone furoate than beclomethasone dipropionate.