A review of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced changes in immunocompetence: 1991 update

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin, more popularly called dioxin or TCDD and referred to in this review as 2,3,7,8-TCDD, is considered the prototype of the polychlorinated dibenzo-p-dioxins (PCDD). The PCDD are true contaminants and are formed primarily as byproducts in the manufacture of materials requiring the use of chlorinated phenols and during the combustion of chlorinated chemical products. From an environmental perspective, the PCDD have been most closely associated with the use of a number of phenolic herbicides, including Agent Orange, which is a 1:1 mixture of the butyl esters of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). 2,3,7,8-TCDD and related PCDD are not produced commercially except in small amounts for research purposes and to date, have no known human benefit. 2,3,7,8-TCDD has been demonstrated to be the most potent and the most biologically active congener among the halogenated aromatic hydrocarbons (HAH), which include polychlorinated and polybrominated biphenyls (PCB and PBB, respectively) and the polychlorinated dibenzofurans (PCDF), in addition to the PCDD. An updated review on the effects of 2,3,7,8-TCDD on immunocompetence is timely from a number of perspectives. First, effects on immune function have been demonstrated to be among the earliest and most sensitive indicators of 2,3,7,8-TCDD-induced toxicity. Second, recent evidence indicates that exposure to 2,3,7,8-TCDD causes changes in innate immunity in addition to the changes in acquired immunity (i.e., which include effects on both cell-mediated and humoral immunity) previously shown to be associated with this chemical. Third, effects on immune function are almost universally observed among the animal species in which it has been evaluated, including some non-human primates. Fourth, effects of 2,3,7,8-TCDD on specific indicators of immune function have been correlated with changes in host resistance capabilities, which are often considered to be more holistic indicators of immunocompetence. Fifth, there are several reports which describe possible effects of 2,3,7,8-TCDD and related compounds (i.e., primarily PBB and PCB) on immune function in humans. It is important to emphasize at the onset that these studies have triggered much controversy, both political and scientific. However, it is equally important to speculate that at least part of the controversy associated with man's sensitivity to the immunological effects of 2,3,7,8-TCDD may be that the most appropriate approaches have heretofore not been applied. This possibility is discussed further in this review.(ABSTRACT TRUNCATED AT 400 WORDS)