title: Glucocorticosteroids inhibit leukotriene production.
abstract: 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 1 microM) with an inhibitory concentration50 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.
authors.affiliation: Creighton University Department of Medicine/Division of Allergy, Omaha, Nebraska, USA.
authors.forename: I C
authors.initials: IC
authors.lastname: Crocker
authors.forename: C Y
authors.initials: CY
authors.lastname: Zhou
authors.forename: A K
authors.initials: AK
authors.lastname: Bewtra
authors.forename: W
authors.initials: W
authors.lastname: Kreutner
authors.forename: R G
authors.initials: RG
authors.lastname: Townley
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D001507:Beclomethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood; D007073:Immunoglobulin E / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000494:pharmacology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011244:Pregnadienediols; C026408:anti-IgE antibodies; D000068656:Mometasone Furoate; D007073:Immunoglobulin E; D001507:Beclomethasone