HYDROQUINONE, A REACTIVE METABOLITE OF BENZENE, INHIBITS NF-KAPPA-B IN PRIMARY HUMAN CD4(-LYMPHOCYTES() T)

Hydroquinone (HQ), a reactive metabolite of benzene, is present in cig arette smoke and is known to inhibit mitogen-stimulated activation of both T and B lymphocytes. Despite extensive study, the underlying mech anism for HQ's immunotoxicity is not clear. NF-kappa B is a transcript ion factor known to regulate the expression of a number of genes criti cal for normal T cell activation. We therefore hypothesized that NF-ka ppa B might be involved in HQ-induced immunosuppression. In this study , we demonstrate that 1 mu M HQ inhibits tumor necrosis factor or indu ced activation of NF-kappa B in primary human CD4(+) T cells. This inh ibition is not accompanied by a loss in viability, and HQ-treated T ce lls maintain other active signaling pathways throughout the exposure d uration. Additionally, the inhibition of NF-kappa B is reversible as H Q-treated T cells regain normal functioning after 72 h in culture. HQ does not appear to alter NF-kappa B directly as preincubation of nucle ar extracts with HQ does not diminish activity of this protein. We fur ther demonstrate that 1 mu M HQ inhibits intracellular IL-2 production in T cells stimulated with phorbol ester but does not alter surface e xpression of CD25 (the alpha-subunit of the IL-2 receptor). These data suggest that NF-kappa B may be an important molecular mediator of HQ' s land benzene's) immunotoxicity. (C) 1998 Academic Press.