Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and structurally similar halogenated aromatic hydrocarbons cause a broad range of immunologic effects in experimental animals including decreased host resistance to infectious disease and suppressed humoral and cell-mediated immune responses. In the mouse, TCDD immunotoxicity has been shown to be an aryl hydrocarbon (Ah) receptor-dependent process. However, despite considerable research, the biochemical and molecular alterations that occur subsequent to Ah receptor activation that lead to altered immune reactivity remain to be elucidated. In addition to immune suppression, TCDD promotes inflammatory responses. This effect may result from an upregulation of the production of inflammatory cytokines such as interleukin-1 and tumor necrosis factor. Nonhuman primates exposed to TCDD show suppressed antibody responses and changes in lymphocyte subsets in the peripheral blood. The immunotoxic effects of TCDD in humans are poorly characterized, and few studies have examined the immune status of individuals with known, documented exposure to TCDD. It is important for laboratory research to focus on defining TCDD-sensitive immunologic biomarkers in animal models that can also be used in human subjects. Understanding the mechanisms that underlie species differences in TCDD immunotoxicity is also of critical importance for extrapolation of effects seen in laboratory animals to man.