Reduced ability of hypothalamic and pituitary extracts from old mice to stimulate thymulin secretion in vitro.

There is substantial evidence that growth hormone (GH) is particularly important in the control of the age-related decline of thymus function. It was therefore of interest: (a) to assess the overall capacity of tissue extracts from mediobasal hypothalamus (MBH), anterior pituitary (AP) and testis, obtained from young (3 months, Yc), middle-aged (13 months, MAc) and old (18 months, Oc) intact C57BL/6 mice to stimulate in vitro the release of thymulin, a Zn-bound immunoregulatory thymic peptide, from pure cultures of mouse thymic epithelial cells (TEC); (b) to perform the same evaluation utilizing MBH, AP and testicular extracts from mice of the same age-range but treated for 45 days with a sc dose of ovine GH (2 micrograms/g body wt) known to stimulate thymulin secretion in vivo. Pituitary hormones were measured by heterologous rat RIAs, whereas thymulin release was estimated by a rosette assay. Untreated animals showed a significant age-dependent increase in the AP content of follicle stimulating hormone but not in other AP hormones. In both control and treated animals, pituitary GH content decreased significantly with age. MBH extracts from C57BL/6 males evidenced thymulin-releasing activity on mouse TEC lines. This activity was maximal in the MBH from young animals and declined with the age of the MBH donors. The thymulin-releasing activity of MBHs from GH-treated mice was higher than that of the control animals and showed a less pronounced decline with age. AP extracts from the same animals showed a higher thymulin-releasing activity than did MBH preparations. This activity showed a progressive age-associated reduction in the APs from untreated mice, whereas in the GH-treated group, an age-related decline was only seen in the old donors. Control testicular extracts had little effect on thymulin release whereas GH treatment induced a definite thymulin-release inhibiting activity in the testicular homogenates of our animals which increased progressively with the age of the testis donors. We conclude that the MBH, AP and testis of the young mouse contain factors able to affect directly the endocrine activity of the thymic epithelium. The amount of these substances declines with age and seems to be modulated by GH.

Altered thymic endocrine activity along with impairments of peripheral zinc metabolism and T-lymphocyte populations are associated with myasthenia gravis: a follow-up study.

Thymic endocrine activity was assessed by a bioassay to determine the basal activity of thymulin (TH), a zinc dependent hormone, and its in vitro reactivation in two different age groups of patients with myasthenia gravis (MG). Before thymectomy, basal TH plasma levels were increased in patients over the age of 50 years. Plasma zinc levels were increased in all patients, this increment being very high in old patients. One year after thymectomy both TH and zinc plasma levels decreased. While zinc plasma levels were within the normal ranges for their respective ages, TH levels were lower in young and higher in old patients than in age comparable controls. Young patients with MG showed increased CD3,DR positive peripheral T-cells as well as lymphocytes with the CD16,CD56 phenotype. An increment of CD3 positive cells along with CD4 and CD16,CD56 positive cells were found in older patients. Thymectomy partially affected blood lymphocyte representation only in young patients, since CD3,DR T-cells decreased one year after surgery. No significant variations in T-cell representation were found in old patients after thymectomy. Immunosuppression in thymectomized patients did not significantly affected TH and zinc plasma levels. Very high levels of TH and the presence of additional alterations in T-lymphocyte subsets in old patients suggested that differential age related pathogenetic immunological mechanisms might be associated with the disease.

Zinc deficiency in elderly patients.

Zinc is needed for growth and development, DNA synthesis, neurosensory functions, and cell-mediated immunity. Although zinc intake is reduced in elderly people, its deficiency and effects on cell-mediated immunity of the elderly have not been established. Subjects enrolled in "A Model Health Promotion and Intervention Program for Urban Middle Aged and Elderly Americans" were assessed for nutrition and zinc status. One hundred eighty healthy subjects were randomly selected for the study. Their mean dietary zinc intake was 9.06 mg/day, whereas the recommended dietary allowance is 15 mg/day. Plasma zinc was normal, but zinc in granulocytes and lymphocytes were decreased compared with younger control subjects. Of 118 elderly subjects in whom zinc levels in both granulocytes and lymphocytes were available, 36 had deficient levels. Plasma copper was increased, and interleukin 1 (IL-1) production was significantly decreased. Reduced response to the skin-test antigen panel and decreased taste acuity were observed. Thirteen elderly zinc-deficient subjects were supplemented with zinc, and various variables were assessed before and after zinc supplementation. Zinc supplementation corrected zinc deficiency and normalized plasma copper levels. Serum thymulin activity, IL-1 production, and lymphocyte ecto-5'-nucleotidase increased significantly after supplementation. Improvement in response to skin-test antigens and taste acuity was observed after zinc supplementation. A mild zinc deficiency appears to be a significant clinical problem in free-living elderly people.

In vitro inhibition of thymulin production in mercury-exposed thymus of young mice.

Lymphocyte differentiation, maturation and peripheral functions are affected by the thymic protein hormone thymulin. Mercury at very low concentrations has been seen to impair some lymphocytic functions causing subclinical manifestations in exposed workers. The present study was performed to test in vitro the effect of mercury on the production kinetics of thymulin using cultures of whole thymuses from young mice. Exposure to mercury (10(-8) M and 10(-6) M) added to the cultures, reduced kinetic thymulin production at all time intervals considered (1, 2, 4, 5 and 6 h) as compared to kinetic thymulin production of thymuses from young control mice. After the first hour the inhibition is more evident at the highest mercury concentration. Thymulin production decreased by 70, 74, 82 and 86% and by 55, 66, 73 and 81% for mercury concentrations of 10(-6) M and 10(-8) M, respectively, after 2, 4, 5 and 6 h. Mercury toxic effect on thymulin kinetics may be directly exerted to thymulin synthesis in epithelial cells, although it is less dramatic than that of cycloheximide (CHX), known as a potent inhibitor of protein synthesis in such cells. The toxic effect of mercury on thymic endocrine activity might cause the subclinical effects on cell-mediated immunological status observed in mercury exposed workers.

[Effect of guzhen recipe on glucocorticoid receptor in senile rate thymocyte].

The effects of Guzhen Recipe (GZ) which composed of Polygonum multiflorum, Cistanche deserticole, Rubus chiagii etc, on the number of thymocyte glucocorticoid receptor (GCR) sites, the GCR nuclear translocation rate, and the activity of serum thymic factors etc in senile rats were observed. The results showed: The number of thymocyte GCR sites, the contents of cytoplasmic protein, nuclear RNA and DNA, the thymus weight/body weight ratio and the serum thymic factors in senile rats were significantly decreased, while thymocyte GCR nuclear translocation rate increased obviously than that of young control rats. GZ, however, was capable of improving the above-mentioned changes of thymus in senile rats markedly, suggesting that GZ might weaken the inhibitory effect of glucocorticoid on the thymus by means of suppressing the translocation activity of GCR from cytoplasm to nucleus in senile rats, thus enhance thymus-dependent immune function in senile rats.

Effect of occupational exposure to elemental mercury in the amalgam on thymulin hormone production among dental staff.

Occupational exposure of dental staff to elemental mercury vapor released from dental amalgam is an issue of concern because of the possible immunological and neurological adverse outcomes. Recently, studies have reported that inorganic mercury induces immunosuppression by decreasing the production of thymus gland hormone (thymulin). This study aimed at investigating mercury body burden in dental staff and the relation of this burden to the potential impact of mercury on thymus gland hormone level (thymulin). Besides, the work aimed at verifying mercury effect on nitric oxide synthetase as a possible mechanism of its immunotoxicity. The study population consisted of a group of dental staff (n = 39) [21 dentists and 18 nurses] and a matched control group (n = 42). Each individual was subjected to detailed occupational and medical history taking and to estimation of urinary mercury (U-Hg) and blood mercury (B-Hg) as indicators of mercury body burden and exposure, respectively. Measurement of total thymulin hormone blood level, and plasma level of nitrite and nitrate (indicators of nitric oxide) was also done. The study showed a significantly increased U-Hg and B-Hg levels in the dental staff compared to their controls. This elevation of mercury body burden was associated with significant reduction in thymulin hormone blood level and nitric oxide parameters. These results were more evident in the group of nurses compared to the dentists. In conclusion, our results show that dentists and dental nurses have significant exposure to mercury vapor and point to the negative impact of mercury on thymus gland functions and confirm the implication that the nitric oxide pathway is a possible mechanism for this impact. Moreover, the study raises attention to the importance of hygiene measures in reduction of exposure to mercury vapor released from dental amalgam.

Age-related thymus involution: zinc reverses in vitro the thymulin secretion defect.

The inevitability of thymic involution in aging has been opened to question by two recent findings. First, it has been demonstrated that the synthesis and/or secretion of one thymic factor, zinc-thymulin (Zn-FTS), is still present, although reduced, in humans over 90 yr of age and in mice over 24 months of age. The major defect resides in the zinc saturation of thymulin, rather than in the synthesis and secretion rate of the polypeptide by the thymus. Zinc pool is in fact reduced in old age. Thymic explants from old mice in vitro for a short period (6 h) produce nearly the same amount of thymulin as young thymuses, but the zinc-bound form is nearly absent. Zinc addition to the cultures fully recovers the defect. These findings clearly suggest that thymic involution is not an intrinsic and irreversible phenomenon, but is largely due to microenvironmental factors, among which zinc is crucial.

[The mechanism of the thymolytic action of anabolic steroids]. / Mekhanizm timoliticheskogo deistviia anabolicheskikh steroidov.

The administration of testosterone and metandrostenolone to male rats in doses of 10 and 20 mg/kg for 10 days produced a decrease of the thymus mass and a reduction of the thymic serum factor content. A phytoecdisteroid ecdisterone not possessing the androgenic activity fails to influence the thymus mass and the content of the thymic serum factor.

Zinc induces thymulin secretion from human thymic epithelial cells in vitro and augments splenocyte and thymocyte responses in vivo.

Zinc is incorporated into zinc-thymulin by the thymus and in this form is a critical hormonal regulator of cellular immunity. In the absence of serum, zinc induces human thymic epithelial cells (TEC) to secrete a factor which promotes the expansion of interleukin-2 (IL-2) receptor positive human peripheral blood lymphocytes in response to a low dose of phytohemagglutinin (PHA). This factor is removed by antithymulin antisera plus filtration and is thus presumed to be zinc-thymulin. Intraperitoneal treatment of hydrocortisone treated aged mice with zinc-thymulin (100 ng/day x 5) resulted in mild augmentation of splenocyte but not thymocyte responses in vitro to IL-1, IL-2, and natural cytokine mixture (NCM) and to PHA and concanavalin A (Con A) (average increase 40%). Like zinc-thymulin treatment, oral ingestion of zinc (72 micrograms/day x 5) resulted in augmentation of splenocyte IL responses; in contrast, it augmented thymocyte responses to all stimuli (average increase 100%). These preliminary experiments indicate that treatment with zinc may have immunotherapeutic relevance, particularly in the aged and stressed organism.

[Effect of thymostimulin on endocrine thymus function in thyroidectomized rats during suppressive hormone therapy]. / Vplyv tymostymulinu na endokrynnu funktsiiu tymusa shchuriv pisla tyreoïdektomiï za umov supresyvnoï hormonoterapiï tyroksynom.

Due to disorders of hormonal balance in the organism, a decrease in thymic endocrine function occurred in rats after thyroidectomy. After removing the thyroid gland, we observed 1,3-2,2-fold decrease in the level of thymic hormone thymulin in the blood serum. When thyroxin was applied at a suppressive dose, endocrine function of the thymus did not restore. Injections of thymostimulin (Tp1) or its combination with thyroxin to thyroidectomized animals restored the level of thymulin up to the level in the intact rats due to effects of either injected preparation or induction of substances possessing thymosine-like activity.