Distribution of age-related thymulin titres in normal subjects through the course of life

Consolini, Rita; Legitimo, Annalisa; Calleri, Angelica; Milani, Monica

doi:10.1046/j.1365-2249.2000.01315.x

Cited by 23 publications

(18 citation statements)

References 22 publications

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“…Circulating levels of this molecule fall sharply in humans affected by pathologies such as acquired immunodeficiency syndrome (17) and DiGeorge syndrome, a syndrome characterized by the congenital absence of the thymus and parathyroid glands (18), as well as during normal aging (6). Thymulin, which is exclusively produced by the thymic epithelial cells (9), exerts a controlling feedback effect on its own secretion (28).…”

Section: Discussionmentioning

confidence: 99%

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Goya¹,

Reggiani²,

Vesenbeckh³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Integrity of the thymus during perinatal life is necessary for a proper maturation of the pituitarygonadal axis in mice and other mammalian species. Thus congenitally athymic (nude) female mice show significantly reduced levels of circulating gonadotropins, a fact that seems to be causally related to a number of reproductive derangements described in these mutants. Interestingly, a number of in vitro studies suggest that the thymic peptide thymulin may be involved in thymus-pituitary communication. To determine the consequences of low serum thymulin in otherwise normal animals, we induced short (8 days)-and long (33 days)-term thymulin deficiency in C57BL/6 mice by neonatally injecting (intraperitoneally) an anti-thymulin serum and assessed their circulating gonadotropin levels at puberty and thereafter. Control mice received an irrelevant antiserum. Gonadotropins were measured by radioimmunoassay and thymulin by bioassay. Both long-and short-term serum thymulin immunoneutralization resulted in a significant reduction in the serum levels of gonadotropins at 33 and 45 days of age. Subsequently, we injected (intramuscularly) an adenoviral vector harboring a synthetic DNA sequence (5′-ATGCAAGCCAAATCTCAAGGTGGATCCAACTAGTAG-3′) encoding a biologically active analog of thymulin, methionine-FTS, in newborn nude mice (which are thymulin deficient) and measured circulating gonadotropin levels when the animals reached 52 days of age. It was observed that neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and prevented the reduction in circulating gonadotropin levels that typically emerges in these mutants after puberty. Our results indicate that thymulin plays a relevant physiological role in the thymuspituitary-gonadal axis.

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Section: Discussionmentioning

confidence: 99%

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Goya¹,

Reggiani²,

Vesenbeckh³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Purified or synthetic thymulin and human or animal sera containing thymulin activity normalize the azathioprine sensitivity, which is lacking in splenocytes of ATx mice. Details of the assay used here with minor modifications have been described elsewhere [38, 39, 40, 41]. …”

Section: Methodsmentioning

confidence: 99%

“…The presence of inhibitory molecule against thymulin was evaluated in 10 out of 18 patients and in 22 age-matched normal subjects by the method of Bach and Beaurain [42]. The method is based on the capacity of sera to inhibit the biological activity of synthetic thymulin (Sigma, Milan, Italy) in the rosette inhibition assay, as previously described [41]. …”

Section: Methodsmentioning

confidence: 99%

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Immunological Evaluation of Patients with Beta-Thalassemia major

Consolini

Calleri²,

Legitimo³

et al. 2001

Acta Haematol

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Abnormalities in the immune system and zinc homeostasis in patients with β-thalassemia major (TM) have been reported. Since zinc ion is essential for the efficiency of the immune system and is required to induce biological activity to thymulin (Zn-FTS), a biochemically defined thymic hormone, we investigated the plasma levels of zinc and both active thymulin (Zn-FTS) and total zinc saturable thymulin (Zn-FTS+FTS) in 18 patients with TM aged between 2 and 31 years and 22 normal controls of the same age. Inhibitory molecules anti-thymulin and the distribution of lymphocyte subsets were also analyzed. Patients with TM presented significantly lowered plasma zinc and thymulin levels when compared to normal subjects. The significant enhancement of the active form of the hormone after zinc addition in vitro suggests that low thymulin values found in TM are due not to a thymic failure in synthesizing and secreting the thymic hormone, but a defect in zinc saturation of the hormone. An impairment of cell subset distribution was also demonstrated. This study shows that zinc and thymulin deficiency contribute to the complex mechanisms underlying immune dysfunction in TM.

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“…At present we know that thymulin production is strongly influenced by the neuroendocrine system (Fabris and Mocchegiani, 1985;Dardenne et al, 1989) and that its serum level in humans and other mammals is age-dependent. (Bach and Dardenne, 1972;Bach and Dardenne, 1973;Consolini et al, 2000). Thymulin is capable of inducing some markers of T cell differentiation (Dardenne et al, 1978;Incefy et al, 1980), to restore some T cell functions , improve some endocrine parameters (Goya et al, 2007) and recently, it has become clear that this thymic factor possesses important antiinflammatory and analgesic properties (Safieh-Garabedian et al, 1982;Safieh-Garabedian et al, 1983;Dardenne et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical evidences showing the presence of thymulin containing cells located in involuted thymus and in peripheral lymphoid organs

et al. 2010

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Thymulin is a well-characterized thymic hormone that exists as a nonapeptide coupled to equimolar amounts of Zn 2+ . Thymulin is known to have multiple biological roles, including T cell differentiation, immune regulation, and analgesic functions. It has been shown that thymulin is produced by the reticulo-epithelial cells of the thymus, and it circulates in the blood from the moment of birth, maintain its serum level until puberty diminishing thereafter in life. To study the localization of this hormone, we prepared polyclonal and monoclonal antibodies against the commercial peptide and utilized immunocytochemical techniques for visualization. The results indicate that thymulin stains the thymic reticular cells, the outer layers of Hassall´s corpuscles and a large round cellular type, which is keratin-negative and does not show affinity for the common leukocyte antigen (CD-45). In mice, this thymulin-positive cell remains in the thymus throughout life and even appears in relatively increased numbers in old involuted thymi. It also appears in thymusdependent areas of the spleen and lymph nodes, demonstrating that at least one of the thymus cells containing this peptide can be found in peripheral lymphoid tissue.

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Distribution of age-related thymulin titres in normal subjects through the course of life

Cited by 23 publications

References 22 publications

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice

Immunological Evaluation of Patients with Beta-Thalassemia major

Immunohistochemical evidences showing the presence of thymulin containing cells located in involuted thymus and in peripheral lymphoid organs

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