Allergen-stimulated leukotriene B4 and interleukin-8 levels in patients with asthma and allergic rhinitis-modulation by a lipid pathway inhibitor.
BACKGROUND
Leukotriene B4 (LTB4), a potent chemokinetic mediator for neutrophils, is enhanced by interleukin-8 (IL-8) and may play a key role in the inflammatory response of asthma.


OBJECTIVE
The aim of the present study was to investigate whether zileuton, a 5-lipoxygenase antagonist known to inhibit LTB4 production and recruitment of eosinophils/neutrophils in bronchoalveolar fluid, could affect the production of LTB4 and IL-8 by allergen-stimulated peripheral blood mononuclear cells in vitro from patients with asthma and/or allergic rhinitis.


METHODS
Peripheral blood mononuclear cells were isolated using Ficoll-Hypaque density gradient from 14 subjects (2 with asthma, 11 with asthma and allergic rhinitis, and 1 with allergic rhinitis) and were stimulated by selected allergens (grass, tree, mite, and mold) in the absence or presence of 1 and 10 microM of zileuton. Supernatants were collected and assayed for LTB4 and IL-8 levels using RIA and ELISA, respectively.


RESULTS
Levels of LTB4 were significantly elevated in peripheral blood mononuclear cells stimulated with mold, grass, and tree compared with the unstimulated control group (P<.05). Levels of IL-8 were significantly elevated in all allergen-stimulated peripheral blood mononuclear cells, except mold, compared with the unstimulated control group (P<.05). Zileuton significantly reduced production of LTB4 by mold and tree-stimulated peripheral blood mononuclear cells. By contrast, no effect of zileuton on IL-8 production was observed in allergen-stimulated peripheral blood mononuclear cells.


CONCLUSIONS
The zileuton-induced attenuation of LTB4 production by allergen-stimulated peripheral blood mononuclear cells from patients with asthma and/or allergic rhinitis occurs independently from the allergen-stimulated IL-8 production.
Frieri
M
M
Department of Medicine, Nassau County Medical Center, State University of NY at Stony Brook, USA.
Therattil
J M
JM
Zitt
M
M
Bouboulis
D
D
Wang
S F
SF
Lark
G
G
Schaefer
P A
PA
Sansone
G
G
D000328:Adult; D000368:Aged; D000485:Allergens / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism*; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012221:Rhinitis, Allergic, Perennial / Q000378:metabolism*; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism*
D000485:Allergens; D016209:Interleukin-8; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; C063449:zileuton; D006918:Hydroxyurea