Thymic hormones

Reconstitution of T-ceU deficiencies with thymic hormones has not been successhil even though the various hormone preparations induce prothymocyte differentiation and functions of mature T-ceUs. They do not regulate the maturation of thymocytes in the thymus. In contrast, IL-2, endotoxin, thymic epithehal cell products, but not interleukin 1, were found to promote functional maturation of immature thymocytes. Two classes of dmgs show thymomimetic actions (Table 2). Levamisole [14769-73-4], sodium salt of diethyl dithiocarbamate (imuthiol) and certain... 

Fok, K.-F., Ohga, K., Incefy, G.S., and Erickson, B.W. (1982) Antigenic specificity of two antibodies directed against the thymic hormone serum thymic factor (FTS). Mol. Immunol. 19, 1667-1673. 

Reproductive toxicity to 2,3,7,8-TCDD has been demonstrated in animals. "" The effects include pre- and postimplantation losses in females, morphologic and functional changes in male and female reproductive organs, and hormonal imbalance in both sexes. A number of developmental effects have been observed in animals acutely exposed to 2,3,7,8-TCDD by the oral route. Effects observed in offspring of animals include cleft palate, kidney anomalies, immune system damage (thymic atrophy and immunosuppression), impaired development of the reproductive system, decreased growth, and fetal/newborn mortality. 

There are many natural and biological macromolecules that possess anticancer activity. Cytokines, topoisomerase inhibitors, monoclonal antibodies, thymic hormones, cell growth inhibitors, and enzymes have been used [68], They have been recently reviewed [59,69] and their detailed description is beyond the scope of this article. The main problems connected with the administration of such natural macromolecules is their short intravascular half-life, immunogenicity, and sometimes poor solubility. Their modification with synthetic macromolecules can dramatically increase their therapeutic potential as described below. 

Several reports have described the anticancer activity of curcumin in a variety of cancer cell lines. In vitro studies have established the activity for curcumin against breast, gastric, hepatic, pancreatic, colorectal, urinary bladder, kidney, prostate, cervical, ovarian, uterine, lung, oral, thymic, and skin cancers. Besides these cancer types, curcumin has shown in vitro therapeutic efficacy against hematological cancers including leukemia, lymphoma, and multiple myeloma. One of our early studies established that the antiproliferative effect of curcumin in human breast cancer cell lines, including hormone-dependent, hormone-independent,... 

While thymic hormones are licensed in Europe and Asia, their use has not been approved in the USA. Recent clinical trials have demonstrated some effectiveness of thymosin-c/l plus IFN- in treating hepatitis B and C. 

Despite the uncertainty in the mechanism of hormone-induced lymphocytolysis, cultured cells of mouse and human origin have been very useful for obtaining resistant cell variants. Mostly, three cell culture lines have been used S49.1 and WEHI-7 mouse lymphoma cells of thymic origin [43,44] and human CEM-C7 lym-... 

The mechanism by which zinc mediates Immune function is not clear the depression of DNA synthesis during zinc deficiency is implicated (9. McCaffrey et al. (97) demonstrated that a zinc-containing DNA polymerase is present in the thymus but does not appear in the mature T cell. A reduction in thymus tissue caused by zinc deficiency would adversely affect the immunocompetence of thymocytes. This hypothesis has been confirmed in experiments where a sharp drop in the thymic hormone is induced by zinc deficiency. 

CaBPs Neurite extension Chemotactic activity Thymic hormone activity Extracellular matrix component... 

Thymic regrowth and reactivation of thymic endocrine activity may occur in older animals by different endocrinological or nutritional manipulations than in young animals. Intrathymic transplantation of pineal gland or treatment with melatonin, implantation of a growth hormone (GH) secreting tumor cell line or treatment with exogenous... 

Diets that are low in protein, zinc, selenium, vitamin Bg, and fat may collectively depress immune function. This type of diet may be associated with either a low-caloric-intake diet or low-fat, low-meat-products diet. Zinc is an essential trace element for many biological functions, including immune functions. Indeed, zinc is required for the biological activity of a thymic hormone, called thymulin in its zinc-bound form, and is important for the maturation and differentiation of T-cells. With advancing age, zinc, thymic functions, and peripheral immune efficiency show a progressive decline. Supplementing zinc in old age restores immune efficiency. 

Argani P, Erlandson RA, Rosai J. Thymic neuroblastoma in adults Report of three cases with special emphasis on its association with the syndrome of inappropriate secretion of antidiuretic hormone. Am J Clin Pathol. 1997 108 537-543. 

High levels of stress combined with lack of sleep or distorted wake/sleep cycles (e.g., shift work) leads to elevated levels of circulating cortisol. Cortisol depresses the synthesis and release of thymic hormones resulting in compromised development of T lymphocytes and a depressed immune response. Light inhibits the production of melatonin so its level falls when individuals have inadequate sleep. This reduces the melatonin-dependent inhibition of CRH release which amplifies the increase in circulating cortisol. The stress induced immunosuppression is therefore enhanced and prolonged. 

Immunohistochemical studies using specific antisera to a number of well-characterized thymic polypeptides have confirmed that it is the thymic epithelial cells that are the major hormone-producing cells of the thymus. Although most thymic polypeptides are found in both medullary and subcap-sular cortical epithelial cells, some are produced almost exclusively by epithelial cells localized in the subcapsular region (Hirokawa et al., 1982) (Fig. 5). The precise cells of origin for each of the well-characterized thymic polypeptides will be discussed in detail later in this article (see Section 6). 

In this section we will review the biochemical and biologic properties of the well-characterized thymic preparations. It should be stressed that although many different thymic factors have been described that can induce T cell differentiation in vitro and/or in vivo in various experimental systems, very few have satisfied all of the requirements for categorization as true thymic hormones. Indeed, detailed thymectomy and thymus reimplantation studies to establish the absolute thymus dependency of circulating bioactivity have only been performed for thymulin (Bach et al., 1972 Bach and Dardenne, 1973). Although thymosin otj, thymosin P4, and thymopoietin are all detectable in serum, strict thymus dependency has not, at this time, been completely established. 

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