ABSTRACT
The relationship of air pollutants with the increasing prevalence of allergic diseases is a matter of concern in developed countries. In this study, the immunomodulatory effects of mono-, di-, and trimethylphenols in mice were examined as regards two aspects. First, whether or not these chemicals act as sensitizers was evaluated by local lymph node assay. Of the 13 methylphenols tested, three dimethylphenol isomers (2,4-DMP, 2,5-DMP, and 3,4-DMP) were found to induce auricular lymphocyte proliferation after dermal application on both ears of mice. Cytokine production patterns in the supernatants of cultured auricular lymphocytes from mice showed these methylphenols to be contact sensitizers. Second, the effects of methylphenols on cytokine production profiles were examined using cultured splenocytes from immunologically naive mice. Under subtoxic conditions, eight methylphenols inhibited interferon-gamma (IFN-gamma) production significantly, while the effect on intreluekin-4 (IL-4) production was moderate, resulting in higher IL-4/IFN-gamma ratios in all of the tested chemicals, with the most prominent effect shown by 2,6-DMP. These results suggest that several methylphenols, especially dimethylphenol isomers, have potencies that affect the immune system, being immunogens themselves or modulators of the Th1/Th2 cytokine balance.
Subject(s)
Immunologic Factors/pharmacology , Phenols/pharmacology , Spleen/drug effects , Spleen/immunology , Xylenes/pharmacology , Animals , Cell Growth Processes/drug effects , Immunologic Factors/immunology , Interferon-gamma/immunology , Interleukin-4/immunology , Local Lymph Node Assay , Male , Mice , Mice, Inbred BALB C , Phenols/immunology , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunology , Xylenes/immunologyABSTRACT
We describe a novel method for the determination of three kinds of dimethylbenzylmercapturic acids (DMM) and six kinds of dimethylhippuric acids (DMH), found in urine as metabolites of trimethylbenzenes, based on liquid chromatography/electrospray ionization tandem mass spectrometry. A solid-phase extraction procedure was used for the extractions of DMM and DMH from a urine sample, and the separation was performed on a reversed-phase C(30) column. The analytes were ionized by electrospray in the positive-ion mode. Operating in the multiple reaction monitoring mode, the linearity of the relative mass spectrometric responses to the internal standard versus analyte concentrations were established in the range 0.1-100 ng ml(-1). The extraction procedure was rapid and the relative standard deviations were below 5%. The detection limits of DMM and DMH in the urine by the proposed method were in the ranges 0.26-0.41 and 0.42-2.0 ng l(-1), respectively. Furthermore, DMM and DMH were detected in a urine sample from an individual who did not suffer from occupational exposure to trimethylbenzenes, by using this method.