Species and strain comparisons of immunosuppression by 2-methoxyethanol and 2-methoxyacetic acid

Abstract

2-Methoxyethanol (ME) and its principal metabolite 2-methoxyacetic acid (MAA) have been shown in our laboratory to be immunosuppressive in male Fischer 344 rats. In this study several strains of 12-week-old female rats and mice were used to compare the immunosuppressive activity of equimolar concentrations of ME and MAA on the trinitrophenyl-lipopolysaccharide (TNP-LPS) antibody plaque-forming cell (PFC) response, which we previously demonstrated to be a sensitive end point. Female inbred Lewis, Fischer 344 and Wistar/Furth, and outbred Sprague-Dawley rats were dosed by gavage with either ME or MAA at dosages of 0.33 to 2.64 mmol/kg/day for 10 consecutive days. Female inbred C3H and C57BL/6J, hybrid B6C3F 1, and outbred CD-1 mice were similarly dosed with equimolar dosages of 0.66 to 5.28 mmol/kg/day ME or MAA. All animals were immunized on day 9 of dosing and PFC responses evaluated 3 days later. Suppression of the PFC response was observed in all strains of rats at 2.64 mmol/kg/day ME or MAA. Lewis and Wistar/Furth rats were found to be the most sensitive strains with suppression at levels as low as 0.66 mmol/kg/day ME or MAA. While ME and MAA dosing resulted in suppression of the TNP PFC response in all the rat strains tested, such treatment did not suppress this PFC response in any of the mouse strains examined. These results indicate that under the conditions of this study rats, but not mice, are immunosuppressed by ME and MAA exposure, and that the susceptibility to immunosuppression differs among rat strains.