Dioxin immunosuppression

Hinsdill, R., Couch, D., and Speirs, R., Immunosuppression in mice induced by dioxin (TCDD) in feed, J. Environ. Pathol. Toxicol., 4, 401, 1980. 

Lawrence, B.R and Vorderstrasse, B., A kinetic study of the recall response to influenza vims infection in mice exposed to the immunosuppressive pollutant dioxin, Toxicol. Sci., 79, 304, 2004. 

A particularly potent immunosuppressive chemical is TCDD, dioxin. This inhibits the differentiation of T cells by damaging the epithelial cells in the cortex of the thymus. These cells are involved in the maturation of T cells. A receptor is involved with this toxic effect, the AHR receptor, to which TCDD binds very strongly. The receptor is expressed in the thymus. Mice, which to do not express this receptor, do not show this particular toxic effect of TCDD even at 10 times higher doses. 

Dioxins - global superecotoxicants, which have strong mutagenic, immunosuppressive, carcinogenic, teratogenic, and embryotoxic activity. 

Clark GC, Blank JA, Germolec DR, et al. 1991a. 2,3,7,8-Tetrachlorodibenzo-p-dioxin stimulation of tyrosine phosphorylation in B lymphocytes potential role in immunosuppression. Mol Pharmacol 39 495-501. 

Holsapple MP, McCay JA, Bames DW. 1986b. Immunosuppression without liver induction by subchronic exposure to 2,7-dichlorodibenzo-p-dioxin in adult female B6C3F1 mice. Toxicol Appl Pharmacol 83 445-455. 

Kerkvliet NI, Steppan LB, Brauner JA, et al. 1990a. Influence of the Ah locus on the humoral immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) evidence for Ah receptor-dependent and Ah receptor independent mechanisms of immunosuppression. Toxicol Appl Pharmacol 105 26-36. 

Vecchi A, Sironi M, Canegrati M, et al. 1983b. Immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the strains of mice with different susceptibility to induction of aryl hydrocarbon hydroxylase. Toxicol Appl Pharmacol 68 434-441. 

There is a very broad range of toxic effects of dioxins. Many of the congeners can induce toxic responses at very low dose. The most sensitive effects are immunosuppression, developmental and reproductive toxicity, as well as neurological behavioral effects. Carcinogenic effects are induced at higher exposure. TCDD was considered a complete carcinogen by the International Agency for Research on Cancer, IARC [115]. 

There is evidence of immunosuppressive effects due to interference by dibenzo-p-dioxin and/or dibenzofuran with the chemical properties of pentachlorphenol (SEDA-11, 485) (40). 

Polyhalogenated aromatic hydrocarbons TCDD (2,3,7,8-tetrachlorodibenzo p dioxin), PBB (polybromated biphenyls), PCDF (polychlorinated dibenzofuran), PCBs (polychlorinated biphenyls), hexachloro benzene, 2,4- dichlorophenol Appears to correlate with carcinogenic effect. Case studies for PCB and organochlorine pesticides resulted infections associated with immunosuppression... 

Dioxin-like compounds are those chemicals that act as ligands for the aryl hydrocarbon receptor (AhR), which appears to be present in most vertebrate classes92. The AhR functions as a ligand-activated transcription factor and is responsible for most of the toxic consequences of dioxin-like compounds150, which can be diverse and include cardiovascular dysfunctions, immunosuppression and embryotoxicity24. Usually, the most potent ligand for the AhR and the most toxic compound is TCDD. Some important classes of ecotoxicants contain members that are AhR active (Table 4). 

At other level, it has implicated chlorophyllins in conjunction with chitosan (chl-chitosan) in the reduction of the body burden of environmental dioxins, by excretion in the feces [56]. Dioxins are the most toxic artificial compounds that mainly enter in the human body through the food. They have usually long half-lives and accumulate in the adipose tissue. The adverse effects of dioxins in the human body are the following teratogenicity, reproductive toxicity, immunosuppression, hepatotoxicity. 

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