Thymus involution

Apart from general toxic action, dioxins, in particular 2,3,7,8-TCDD, cause thymus involution and immunodeficiency, however, less pronounced than in die event of HIV infection. Experiments with mice have shown that cell-mediated immunity was suppressed even at doses of 0,04 mcg/kg. 

Indirect effects mediated by the adrenal gland thymus involution and an increase in glucose utilization... 

The CRF-overexpressing mice are a genetically engineered strain with more than the normal number of copies of the CRF-encoding gene inserted in their genome. Compared with their wild-type counterpart, these animals show increased anxiety they also have some of the abnormalities seen in hypercortisolemic patients, such as adrenal hypertrophy, marked thymus involution and increased abdominal fat (Beckmann et al.. 2001). They have increased blood levels of cortisol and represent an animal model of hypercortisolemia IStenzel-Poore et al.. 1992. 1994 Holmes, 2001). 

Penninks A, Kuper F, Spit BJ, et al. 1985. On the mechanism of dialkyltin-induced thymus involution. Immunopharmacology 10 1-10. 

Biological studies on 16a-hydroxy-hydrocortisone [15] have demonstrated that this type of corticoid derivative still maintains a considerable activity in the usual types of assays (glycogen deposition, thymus involution and anti-inflammatory tests). It was therefore of interest to prepare the 16a-hydroxy derivatives of the more potent 9a-halo steroids. 

In a cohort of apparently healthy and well-nourished elderly women, total T (CD3 ), T-helper (CD4 ), or T-cytotoxic (CD8 ) cell number, NK cell number, cytotoxicity, phagocytosis, and subsequent oxidative burst were similar to values in young women. However, they had lower T-cell proliferation responses and significantly reduced response to phytohemagglutinin (Krause et al., 1999). T-cells show the largest age-related differences in distribution and function with aging with thymus involution as the apparent underlying cause (Shinkai et al., 1998). 

Simple alkyl esters also proved virtually inactive. Consequently, the 17/3-chloromethyl ester was held constant and 17a-carbonates with different substituents on the steroid skeleton were varied for further investigation. Loteprednol etabonate, and some of the other soft steroids, provided a significant improvement of the therapeutic index determined as the ratio between the anti-inflammatory activity and the thymus involution activity (114, 117,118). Furthermore, binding studies using rat lung cytosolic corticosteroid receptors showed that some of the compounds approach and even exceed the binding affinity of the most potent corticosteroids known. 

Both prednisone and prednisolone were found to have adrenocortical activity (measured by eosinopenic response, liver glycogen decomposition, and thymus involution in adrenalectomized mice). In these tests, prednisone and prednisolone were found to be three- or fourfold more potent than cortisone and hydrocortisone. Antiphlogistic strengths in human subjects were similarly augmented, but their electrolyte activities were not proportionately increased. 

A8 Andersson, J. and Darzynkiewicz, Z. Nucleoprotein changes and uridine incorporation in rat thymus lymphocytes. I. Cellular characterization of age-dependent thymus involution. II. Effect of treatment with anti-thymocyte serum in vitro. Exp. Cell Res., 75, 410-416 417-423 (1972)... 

Baez-Saldana A and Ortega E. Biotin deficiency blocks thymocyte maturation, accelerates thymus involution and decreases nose-rump length in mice. J. Nutr. 134 1970-1977 (2004). 

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