Benzene and its metabolites have been involved in the pathogenesis of chronic
lung inflammation and allergic disorders such as
bronchial asthma. However, the effects of these
xenobiotics on human basophils, key cells in the development of respiratory
allergy, have not been investigated. We examined the effects of
hydroquinone (HQ) and
benzoquinone (BQ), two important chemicals implicated in
benzene toxicity, on the release of preformed (
histamine) and de novo synthesized mediators (
cysteinyl leukotriene C4,
LTC4, and IL-4) from human basophils. Preincubation of basophils purified from normal donors with HQ (3-100 microM) inhibited up to 30% histamine release induced by
anti-IgE and up to 55% of that induced by the Ca2+
ionophore A23187. HQ had no effect on histamine release induced by formyl-
methionyl-leucyl-phenylalanine (
f-Met-Leu-Phe). Preincubation of basophils with BQ (3-100 microM) resulted in the concentration-dependent inhibition of histamine release (up to 70%) induced by
anti-IgE,
A23187 and
f-Met-Leu-Phe. HQ completely suppressed the de novo synthesis of
LTC4 from basophils challenged with
anti-IgE or
f-Met-Leu-Phe and the production of
IL-4 in cells stimulated with
anti-IgE. These results indicate that two major
benzene metabolites, HQ and BQ, inhibit the release of proinflammatory mediators and Th2-promoting
cytokines from basophils activated by different stimuli. These results suggest that
benzene metabolites interfere with multiple intracellular signals involved in the activation of human basophils.