2,3,7,8-Tetrachlorodibenzo-p-dioxin co-stimulates Staphylococcal Enterotoxin β (SEB) cytokine production and phenotypic cell cycling in Long–Evans rats

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that is considered to be a potent immunotoxicant. In the present study, we examined the effect of 25 μg\\kg TCDD on cytokine production and T lymphocyte phenotype, cell cycling and receptor activity in female Long–Evans rats that had been injected with 50 μg of Staphylococcal Enterotoxin B (SEB). In the SEB-injected rats, TCDD increased the serum levels of interleukin-2 (IL-2) but did not affect the serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) or tumor necrosis factor (TNF). The ability of spleen cells and peritoneal cells to produce cytokines in response to SEB restimulation in vitro was also evaluated. TCDD exposure significantly enhanced IL-2 production by spleen cells from SEB-primed rats after 6 h or 24 h in cultures co-stimulated with SEB in vitro. However, TCDD treatment did not alter the production of IL-1, IL-6 or TNF in these cultures. Although TCDD did not influence the production of IL-6 and TNF in peritoneal cells from SEB-primed rats with SEB restimulation in vitro, IL-1 production was significantly increased at 2 h. Both the kinetics and extent of SEB-induced IL-2 receptor (IL-2R) and T-cell receptor (TCR) expression on CD4 + cells was unaffected by TCDD. TCDD did not significantly alter the percentage or the total numbers of CD4 + and CD8 + subpopulations at various times after SEB injection. However, flow cytometric analysis showed that TCDD exposure increased the percentage of both CD4 + and CD8 + cells cycling in the S and G2M phase. TCDD, in the absence of SEB priming, did not affect any of the immune parameters tested. Nevertheless, collectively these results showed that TCDD can enhance the production of IL-2 and the percentage of CD4 + and CD8 + cells cycling in SEB-exposed Long–Evans rats. Histopathologically, there were no observable effects of SEB on lymphoid organs while thymic atrophy and diffuse hepatocellular hypertrophy was observed in the TCDD-treated animals.