Phthalates Potentiate the Response of Allergic Effector Cells

Abstract

Several studies strongly indicate that there is a positive correlation between the level of urbanization and industrial development and the incidence of allergic diseases. Increasingly more time is being spend in an indoor environment and the existence of allergy-promoting factors in private homes and public buildings has been suggested (Aas et al. 1997; Poulsen et al. 2000). New chemicals such as plasticizer-containing plastics have been introduced to the indoor environment. The plasticizers are not covalently bound to the plastic matrix and can therefore be released from products and become airborne or absorbed to small dust particles leading to human exposure by inhalation (Oie et al. 1997; Jaakkola et al. 1999; Clausen et al. 2003). Recently, a study in a murine model suggested phthalates and monophthalates to stimulate the IgE and IgG1 production (Larsen et al. 2002). Yet another study shows an increase in intracellular Ca2π concentration and degranulation in the rat basophillic leukemia cell line RBL-2H3 when stimulated with diphthalates (Nakamura et al. 2002). To test for a possible effect in man we have used the basophil histamine release assay, which models the inflammatory part of allergic disease. We examined five commonly used diphthalates and their corresponding five monophthalates, which are the primary metabolites after hydrolysis. Peripheral blood mononuclear cells containing 0.1–1% basophils obtained from freshly drawn blood or blood bank buffy coats were preincubated with monoor di-phthalate (5–500 mM) for 15 to 60 min. (mono-n-butyl phthalate (MBuP), mono-n-octyl phthalate (MOP), mono-iso-nonyl phthalate (MINP) and mono-isodecyl phthalate (MIDP) were all synthesised at the National Institute of Occupational Health, Copenhagen, Denmark. The rest of the monoand diphthalates were obtained from Tokyo Kasei Organic Chemicals (TCI), Tokyo, Japan (Larsen et al. 2001 & 2002). Subsequently, phthalate was removed by washing and the cells stimulated with anti-IgE