Benzene Metabolites Inhibit the Release of Proinflammatory Mediators and Cytokines from Human Basophils

Abstract

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 C 4 , LTC 4 , and IL-4) from human basophils. Preincubation of basophils purified from normal donors with HQ (3-100 JIM) 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 ofbasophils with BQ (3-100 JIM) 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 LTC 4 from basophils challenged with anti-IgE or f-Met-Leu-Phe and the production oflL-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.

Cholesterol, Cytokines and Diseases

“…These cells amplify the local inflammatory activity by producing proinflammatory cytokines such as IFN-and CD40 ligand (CD40L, CDI54), which contribute importantly to plaque progression. Adiponectin also directly affects the function of endothelial cells, reducing VCAM-l expression and macrophages, decreasing the expression ofscavenger receptors and the production ofTNF-a (36)(37)(38)(39)(40).…”

Role of Th2 cytokines on the onset of asthma induced by meta‐xylene in mice

“…In particular, substances contributing to the onset and promotion of allergies and asthma include BTX and FA, which are often found indoors . Studies also showed that single exposure to benzene, toluene, and formaldehyde induced airway inflammation, which is directly related to asthma . Exposure to m ‐xylene is known to not only induce wheezing but also aggravate intensity of asthma.…”

“…In other research, benzene inhalation was associated with airway inflammation or pulmonary inflammation. It has been shown to be caused by inflammatory cells different from basophils …”

“…It has been shown to be caused by inflammatory cells different from basophils. 15 Xylene exposure is known to affect various tissues and the central nervous system. In terms of its effects on the lungs, xylene causes not only chest pain and dyspnea but also excessive exposure leads to pulmonary edema.…”

Allergic Inflammation: Role of Cytokines with Special Emphasis on IL-4

“…Pro-inflammatory cytokines, particularly those encoded as chromosome 5q including interleukin (IL)-4, IL-5, and GM-CSF along with, TNF-alpha play a role in allergen-induced.airway leukocyte recruitment and these cytokises canbe generated not only by T cells but also by mast cells and other cells (3)(4)(5). The early cell recruitment within 6 hrs of challenge is likely to be mast cell determined (6)(7), with a potential but undefined contribution from alveolar macrophages as this cell population can generate TNF-alpha and IL-1-beta, inflammatory cells that are of importance to endothelial leukocyte adherence (8).…”