Thymic involution

All dead in 11 days thymic involution and edema gross accumulations of uroporphyrins in liver... 

ARNT.26-37 Mice that did not express ARNT in their T cells did not show thymic involution following TCDD exposure. 

Tomita, S., et. al., T cell-specific disruption of the aryl hydrocarbon receptor nuclear transporter (Amt) gene causes resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymic involution, J. Immunol., 171, 4113, 2003. 

Nickel salts have also been reported to have immunosuppressive properties in rodents, including giving acute thymic involution [389, 390], suppression of T lymphocyte response to T cell mitogens [389], suppression of antibody [389, 391, 392] and interferon production [393] and suppression of natural killer (NK) cell activity [389, 394-397]. 

Wiktor-JedrzeJczak, W., Grzybowski, J., Ahmed, A., and Kaczmarek, L. (1983) Osteopetrosis associated with prematnre thymic involution in grey-lethal mice. In vitro studies of thymic microenvironment. Clinical Experimental Immunology 2, 465-471. 

TCDD or estrogen results in thymic involution and modulation of particular bone marrow stem cell markers (Silverstone et al. 1994). However, the mechanism by which these compounds act are clearly different since potent antiestrogens block the effects of estrogen treatment without affecting... 

Extensive evidence suggests that the immune system is a sensitive target for toxicity of 2,3,7,8-TCDD and structurally related halogenated aromatic hydrocarbons (Kerkvliet 1995). Exposure to 2,3,7,8-TCDD can increase susceptibility to bacterial (Thigpen et al. 1975 Thomas and Hinsdill 1979 White et al. 1986), viral (Clark et al. 1983 House et al. 1990), parasitic (Tucker et al. 1986), and neoplastic disease (Luster et al. 1980). However, the specific immunological functions affected by 2,3,7,8-TCDD in most of the host-resistance models have not been fully defined. Thymic involution is characteristic of exposure to 2,3,7,8-TCDD and structurally related chemicals in all species examined. There is experimental evidence showing that immune suppression in rodents occurs at lower doses of... 

While many a jogger has suggested that exercise can improve his/ her resistance to infectious diseases, conclusive scientific evidence that exercise enhances immune response has yet to be presented. Experimental zinc deficiency in animals may provide a workable model for such investigations. It is well known that exercise induces hypertrophy of adrenal glands with a concomitant increase in the serum concentration of glucocorticoids. Zinc deficiency decreases T cell helper activity and thymic involution followed by a rise in glucocorticoids (98). The observations cited above suggest that it is possible to delineate experimentally the roles of zinc and exercise in immune response. 

In rats, EGME and its metabolite have also been reported to cause thymic involution in the absence of effects on body weight or spleen weight, reduced response to T cell mitogens, depressed production of interleukin-2, and altered response to primary antibody plaque-forming cells. Mice were not affected. 

Oral LD50 values range from 1 to 3gkg in rodents. A dermal LD50 of 1.3gkg was determined in rabbits. An inhalation LC50 of 4600 ppm was determined in mice. In animals, systemic effects from sublethal, or short-term exposures, are kidney damage, thymic involution, depression of blood cell counts, and depression of bone marrow cellularity. 

As the dose level of chronic exposures increases, methoxyethanol becomes immunosuppressive. Thymic involution, decrease of spleen weight, and suppression of various lymphocyte and antibody responses are noted at doses as low as 50 mg kg in rats and mice, although comparison of several studies indicate that rats may be more susceptible than mice. Effects became more severe as the dose level of methoxyethanol increased in the studies. 

The restoration of immune functions of the aged individuals is possible and might be beneficial for them to cope with various diseases associated with aging (Hirokawa, 1997). Physiological thymic atrophy is controlled by both extrathymic and intrathymic factors and is not a totally irreversible process. Tlie process of thymic atrophy might be explained by a further understanding of the relationship between the neuroendocrine and the immune systems (Hirokawa et al., 1994). Although the most obvious age-related structural alteration of the immune system occurs in the thymus, the role of thymic involution in immunosenescence is still not well understood. 

Natural killer cell activity and T-cell-medi-ated immune responses are inhibited in spleens of NiCl2-treated mice (Smialo-wicz et al. 1984, 1985), acute thymic involution develops in NiCl2-treated rats (Knight et al. 1987), and the antigenic responsiveness of splenocytes is impaired (Schiffer et al. 1991). 

Knight JA, Rezuke WN, Wong SHY, Hopeer SM, Zaharia O and Sunderman FW Jr (1987) Acute thymic involution and increased lipoperoxides in thymus of nickel chloride-treated rats. Res Commun Chem Pathol Pharmacol 55 101-109. 

In addition to thymic involution, there are other important age-associated changes in the structure of the lymphoid tissues. The number of mature lymphocytes and plasma cells in the bone marrow markedly increases while the number of germinal centres in the lymph nodes and spleen is reduced with age (Benner et al. 1981, Gonzalez-Fernan-DEZ et al. 1994). 

The toxic effects of synthetic polymers include inhibition of hepatic microsomal oxidase enzymes, stimulation of liver transaminases, hepatosplenomegaly, thymic involution, anaemia, and decrease in bone marrow cells Fortunately, many neutral synthetic polymers do not show toxic effects. For those polymers which exhibit toxic effects, e.g. polyanions, it is sometimes possible to separate the toxicity from antitumour, antiviral and immunological effects In general the toxicity of polyanions increases with molecular weight (particularly for M > 50,000). 

The evidence to date implies that the Ah receptor participates in every biological response to TCDD. For example, studies of stmeture activity relationships among congeners of TCDD reveal a correlation between a compound s specific binding affinity and its potency in eliciting biochemical responses, such as enzyme induction [171]. Furthermore, inbred mouse strains in which TCDD binds with lower affinity to the receptor exhibit decreased sensitivity to dioxin s biological effects, such as thymic involution, cleft palate formation, and hepatic porphyria. While there are a few... 

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