Immunotoxicity of N,N-diethylaniline in mice: effect on natural killer activity, cytotoxic T lymphocyte activity, lymphocyte proliferation response and cellular components of the spleen

We previously found that N,N-diethylaniline increased the frequency of sist er chromatid exchange (SCE) of human lymphocytes to about five times that o f the control value, and was as toxic as cyclophosphamide used as a positiv e control for SCE. To explore whether N,N-diethylaniline affects the functi on of lymphocytes, we evaluated its immunotoxicity using CBA/N mice. The mi ce were divided into four groups and received 0, 100, 200, or 400 mg/kg bod y weight of N,N-diethylaniline by subcutaneous injection. The following ite ms were investigated on days 3 and 7 after injection: body weight, weight o f spleen, number of splenocytes, natural killer (NK) and cytotoxic T lympho cyte (CTL) activities, and concanavalin A (Con A)- and lipopolysaccharide ( LPS)-stimulated lymphocyte proliferation using splenocytes. The following s plenocyte phenotypes were also quantified by flow cytometry: (1) B cells; ( 2) total T cells; (3) CD4(+) and CD8(+) T cells; (4) NK; (5) macrophages an d (6) nucleated erythrocytes. The splenic NK and CTL activities in exposed groups significantly decreased compared to the control in a dose-dependent manner and lymphocytes from the 200 and 400 mg/kg groups showed significant ly higher spontaneous proliferation. The weight of the spleen and number of splenocytes were significantly higher in exposed groups than in the contro l. N,N-Diethylaniline also increased the percentages of macrophages, nuclea ted erythrocytes and B cells in the spleen. On the other hand, N,N-diethyla niline did not affect LPS-stimulated B cell and Con A-stimulated T cell pro liferation, or the percentages of NK, total T, and CD4(+) and CD8(+) T cell s in the spleen or the body weight of mice. The above findings indicated th at N,N-diethylaniline selectively inhibited splenic NK and CTL activity and this inhibition was due to decreased NK and CTL functions, but not due to changes in the numbers of splenic NK and T cells. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.