Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on interleukin-4-mediated mechanisms of immunity.

Because of similarities in the independent actions of the pleiotropic cytokine, interleukin-4 (IL-4), and the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on murine B-lymphocytes suggested in earlier studies, we have investigated whether the immunosuppression mediated by direct exposure to TCDD in vitro is due to an IL-4-like biological activity. In particular, the ability of TCDD to mimic hallmark responses of B-cells to IL-4, such as upregulation of major histocompatibility complex (MHC) antigens of the class II type, increases in cell surface expression of the low affinity form of the Fc receptor for IgE (CD23) and induction of immunoglobulin class switching, was tested. At concentrations that readily suppress B-cell proliferative and antibody-forming cell responses, TCDD failed to demonstrate any of the activities of IL-4 observed in parallel cultures. Further, in experiments in which TCDD was preincubated with B-cells before addition of IL-4, no evidence of increased IL-4 activity was observed. Rather, TCDD preincubation resulted in decreased secretion of IgG1 and IgE in B-cell cultures stimulated to undergo immunoglobulin class switching by incubation with bacterial lipopolysaccharide (LPS) and IL-4. Because TCDD produced comparable suppression of IgM secretion induced by LPS alone (i.e., no IL-4), it appears that TCDD inhibits the formation of fully differentiated B-cells capable of secreting antibody and has no effects on class switching events per se. Coupled with previous reports from this and other laboratories, these observations indicate that TCDD is able to suppress secretion of several classes of immunoglobulin.