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PubMed1992

Radioprotective effects of serum thymic factor in mice.

Serum thymic factor (FTS) reduced mortality of mice after total-body irradiation with 7.56 Gy X rays. The radioprotective effect was achieved by daily repeated subcutaneous injections of 3-100 micrograms FTS, while doses higher than 300 micrograms/day/mouse were neither radioprotective nor toxic. Similarly, degeneration of the spleen was moderated by 3-100 micrograms FTS but not by 500 micrograms FTS in sublethally (3.78 Gy) irradiated mice. Histological examination showed that hematopoiesis was enhanced in the spleen by daily injections of 10 micrograms FTS. Spleen cells from the FTS-treated mice incorporated more [3H]thymidine in culture with or without concanavalin A. The treatment with FTS increased the production of colony-stimulating factor in the spleen as well as in peritoneal macrophage-like cells, and caused a significant increase in the number of granulocyte-macrophage colony-forming cells both in the spleen and in the femoral bone marrow. Furthermore, FTS prevented a decrease in circulating neutrophils in the sublethally irradiated mice. Prominent overshoot recovery of myelopoiesis, which occurred occasionally in sublethally irradiated mice, did not occur in the FTS-treated mice. The decrease in blood erythrocytes was also significantly reduced. These observations imply that this thymic hormone has potential as a radioprotector.

Animals↗
PubMed1990

Influence of growth hormone on thymic endocrine activity in humans.

The thymus produces humoral factors that induce the proliferation and differentiation of T cells which are responsible for cell-mediated immunity. Experimental data have suggested that this thymic hormone production is modulated by the neuroendocrine network and, in particular, by growth hormone (GH) and thyroid hormones. To study the role played by GH in thymic endocrine activity in humans, the circulating level of one of the best known thymic peptides, i.e. thymulin (Zn-FTS), has been determined, after a washout period of 2 weeks without GH treatment, in GH-deficient children before and after a single injection of GH. The basal thymulin level is consistently lower in GH-deficient children than in healthy age-matched controls. A single injection of GH induces a significant increment of the thymulin level for at least 48 h. Since thymulin activity may also depend on zinc bioavailability, on thyroid hormone turnover and on the eventual presence of thymulin-inhibitory substances, all these aspects have been checked. No supporting evidence regarding the existence of these kinds of interferences in GH-deficient children has been substantiated. A positive correlation has been found between the serum level of insulin-like growth factor I, but not of GH, and thymulin activity. These data suggest that GH may directly or indirectly modulate the thymic endocrine function in humans. Whether and to what extent such a modulation is relevant to the functioning of the immune system remains to be ascertained.

Adolescent↗
PubMed1988

Systemic lupus erythematosus in a colony of dogs.

A colony of dogs was obtained by the mating of a female German Shepherd Dog crossbred and a male Belgian Shepherd Dog crossbred, both with systemic lupus erythematosus (SLE). The colony also contained 16 dogs representing F1, F2, and F3 generations. Ten colony dogs had circulating antinuclear antibodies, and 5 of the 10 had clinical signs of SLE. Two F3-generation females had signs of severe SLE. Two dogs had antibodies to extractable nuclear antigen, notably 1 dog had antibodies to Smith (Sm) antigen and 1 had antibodies to Sjogren syndrome A (SSA) antigen. Thymulin (serum thymic factor associated with zinc) titers were generally low in the descendants, but fluctuations were detected within the same dog. In vitro response of lymphocytes from these colony dogs to concanavalin A was maximal for lower mitogenic concentrations, compared with response of lymphocytes from 10 healthy dogs. The suppressive lymphocyte activity in 6 autoimmune colony dogs was diminished in comparison with the activity in 5 nonautoimmune colony dogs and 6 healthy dogs.

Animals↗
PubMed1990

[Increase of circulating levels of thymulin in hyperprolactinemia and acromegaly].

The production of thymulin by the thymic epithelium is under complex control involving the endocrine system. Experimental models have suggested that prolactin (PRL) and growth hormone (GH) participate in this regulation but this has not been documented in humans. Using a bioassay we measured circulating thymulin levels in patients with hyperprolactinemia (n = 21), acromegaly (n = 15), or both (n = 6). Thymulin was elevated in these three groups of patients compared with normal subjects or with patients with pituitary disease but no excess in PRL or GH. Contrasting with observations in control groups, thymulin did not decrease as a function of age in patients. No correlation between thymulin and PRL or GH levels was observed while thymulin and insulin-like growth factor 1 levels were correlated. A new radioimmunoassay used in some patients for thymulin determination yielded similar results. Overall these data demonstrate that PRL and GH are involved in the hormonal control of thymulin production by the thymic epithelium in the human.

Acromegaly↗
PubMedDate not supplied

Thymus and aging: potential of gene therapy for restoration of endocrine thymic function in thymus-deficient animal models.

OBJECTIVE AND BACKGROUND: The aim of the present article is to discuss the potential of gene therapy for thymic hormones as a novel therapeutic strategy to treat dyshomeostatic states associated with athymia, as Di George syndrome, or hypothymic conditions like those associated with AIDS, chronic stress or aging. First we review the advantages of the athymic (nude) mouse as an animal model to implement experimental thymic hormone gene therapy strategies to restore endocrine thymic function. The aging rat, known to be markedly hypothymic, is also considered as an alternative model. METHODS AND EXPECTED RESULTS: The possibility of constructing adenoviral vectors harboring a synthetic gene for the thymic hormone thymulin is discussed. The adenoviral vector so constructed would then be injected intramuscularly in nude mice or senile rats. Transduced myocytes should then begin to act as an ectopic source of thymulin thus restoring circulating thymulin levels to normal youthful levels. CONCLUSION: We conclude that the implementation of thymulin gene therapy should provide novel biotechnological tools that will boost basic studies on the molecular biology of thymulin and would also allow an assessment of the potential of gene therapy to restore circulating thymulin levels in thymodeficient animal models.

Adenoviridae↗
PubMed1982

Absence of variation in facteur thymique sérique activity in moderately and severely malnourished Senegalese children.

Facteur thymique sérique activity was evaluated in relation to different types of malnutrition in Senegalese children aged 5 to 42 months. They were classified in four groups: controls, moderate malnutrition, marasmus, and kwashiorkor, according to anthropometric measurements and clinical examination. The two latter groups were characterized by very depressed levels of total protein, album in, transferrin and prealbumin, and by high cortisol concentrations. Zinc status was marginal in all children. Facteur thymique sérique activity, determined by the rosette assay, was normal in the malnourished patients suggesting that moderate as well as severe malnutrition is not necessarily associated with depressed levels of circulating thymic hormone. These results are discussed in relation to zinc status and infections.

Blood Proteins↗
PubMed1986

Neuroendocrine regulation of thymus hormones: hypothalamic dependence of "facteur thymique serique" level.

The influence of the hypothalamus extract (HE) on the blood level of the "facteur thymique serique" (FTS) was studied. Hypothalami collected from young mice were pooled, homogenated in saline, and centrifuged; finally, the supernatant injected in old or thymectomized mice with no detectable levels of FTS. In the old mice the treatment results in a reappearance of this circulating thymic hormone; in contrast, in adult thymectomized animals, the HE injection was not able to induce FTS activity. When HE donors were pretreated with thymosin fraction 3, known to contain FTS among other active peptides, the capacity of such a hypothalamus preparation to induce reappearance of FTS in old animals is greatly diminished. The data presented here suggest that the capacity of the thymus to secrete FTS depends on a hypothalamic factor, and therefore the absence of this thymic hormone in the aged reflects a failure of the thymus linked to its impaired neurologic control. On the other hand it seems evident that a feedback system operates in order to regulate the release of this hypothalamus stimulatory factor.

Animals↗
PubMed1978

Age, thymic involution, and circulating thymic hormone activity.

Circulating thymic hormone activity and thymic histology were studied in patients undergoing open heart surgery. Plasma thymic hormone activity was measured using a bioassay based upon thymocyte antigen induction on null mouse lymphocytes. Activity was highest at 15-30 yr of age and declined thereafter, being negligible after the sixth age decade. The age-related decline of circulating thymic hormone activity correlated, in general, with progressive thymic involution. However, hormone activity was detected in plasma from some cases with advanced involution, suggesting that the normal young thymus may have considerable functional reserve.

Adolescent↗
PubMed1999

Effects of the thymic peptide thymulin on in vitro and in vivo testicular steroid concentrations in white composite and Meishan boars.

Immuno-peptides may have positive or negative effects on gonadal steroidogenesis, but few have been tested outside of rodent species or in vivo. In Exp. 1, thymulin, a secreted nonapeptide of the thymus, was incubated (1, 10, 100, or 1,000 ng/mL) with testicular minces (sampled at 3, 6, or 12 h) from Chinese Meishan boars of high gonadotropin/testicular steroidogenic function (n = 8) and White composite boars of European origin (n = 8 ) to test the hypothesis that thymulin could augment hCG stimulation of testicular androgen concentrations. Thymulin alone had few effects on androgen concentrations (testosterone, dehydroepiandrosterone+dehydroepiandrosterone sulfate [DHEA+DHEASO4]) in Meishan boar testicular incubates. In minces from White composites incubated with thymulin, testosterone concentrations were generally below control values (P<.05), but DHEA+DHEASO4 concentrations were unaffected. Thymulin had no effect on estrone concentrations in testicular incubates of White composite boars but stimulated estrone concentrations in Meishan testicular incubates. Thymulin plus hCG increased testosterone (3 and 6 h of incubation; P<.05) but not DHEA+DHEASO4 concentrations in White composite testicular incubates. Thymulin plus hCG did not alter androgen or estrogen concentrations from control values in Meishan testicular incubates. In Exp.2 with a protocol similar to that of Exp. 1 for testicular minces from White composite boars (n = 30), thymulin increased testosterone concentrations during the early incubation period (1 to 3 h; P<.05) and depressed testosterone concentrations at later times (6 h; P<.05). Thymulin synergized with hCG in stimulating increases in testosterone and DHEA+DHEASO4 concentrations (P<.05) but had no effect on estrone concentrations in vitro. Thymulin was tested in vivo in boars from three genetic lines selected for high, medium, or normal circulating LH concentrations (Meishan, select White composites, and control White composites, respectively). Injection of thymulin i.v. (4.4, 44.4, or 444.4 ng/kg BW) generally increased circulating testosterone concentrations (2 to 3 h later; P<.01), but the response was dependent on the boar's general circulating LH concentrations and dose of thymulin. Overall results from these studies support the hypothesis of a thymulin augmentation of LH stimulation of androgen increases in vitro and in vivo in the testis of boars.

Animals↗
PubMed1988

Spontaneous familial systemic lupus erythematosus in a canine breeding colony.

A colony of German shepherd dogs was studied in which a high proportion of antinuclear antibody (ANAb) carriers and dogs with systemic lupus erythematosus (SLE)-like signs were found. The titre of serum thymulin and the percentage of circulating T lymphocytes were both low. The incidence of disease decreased down the generations through the introduction of outside sires, thus suggesting a genetic origin for the disease.

Animals↗
PubMed1999

Role of zinc and alpha2 macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma.

Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. Alpha2-macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because alpha2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35-60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2-IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented alpha2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and alpha2-macroglobulin (r = 0.75, P < 0.01, r = 0.78, P < 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in alpha2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency.

Adult↗
PubMed1993

The humoral activity of the avian thymic microenvironment.

The thymic microenvironment (composed of the lymphoepithelial stroma and the secretory products of the thymic epithelium) provides the required milieu for the development of the thymus-derived lymphocytes (T cells). There is limited information characterizing or identifying the active secretory components of the avian thymus. The work discussed here has focused on examination of the presence, regulation, and activity of one of the thymic hormones (thymulin) in the chicken. A thymulin-like product has been shown to exist in chicken serum as assessed by the mammalian bioassay and an ELISA immunoassay; thymectomy removes this product from the serum. Serum thymulin activity has been shown to be directly related to the thyroid status of the chick with the functionally hypothyroid Cornell sex-linked dwarf strain having lower levels than the euthyroid K strain. Alterations in circulating thymulin concentrations produced by daily thymulin injections resulted in an altered profile of the major peripheral blood T cell subpopulations and produced significant changes in the autoimmune pathology present within the Obese strain chicken. These approaches represent preliminary attempts to study the role of thymulin in avian immune development and in immune-neuroendocrine interactions.

Animals↗
PubMed1986

Low circulating thymulin-like activity in children with AIDS and AIDS-related complex.

Thymic secretory function was assessed by determining levels of circulating thymulin-like activity in plasma of 21 pediatric patients infected with the HTLV-III/LAV retrovirus. All the patients had serum antibodies against p41 antigens of HTLV-III on Western blot analyses. In accordance with the latest definition established by the Centers for Disease Control, 14 patients had the acquired immunodeficiency syndrome (AIDS) and the remaining 7 were classified as having AIDS-related complex. Their ages ranged from 1 to 7 years, with 10 being less than 1 year of age. Circulating thymulin activity, normally highest in healthy children under 15 years of age, was undetectable in 11 patients and below normal range for age in the remaining. OKT4/OKT8 ratios of T-cell subsets in peripheral blood were below normal in the majority of patients. Our findings suggest that thymic epithelial injury may be an early event in HTLV-III/LAV-related disease and may precede the development of clinical and/or immunologic aberrations.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Modulation of thymic endocrine function by thyroid and steroid hormones.

The thymic epithelium is responsible for the secretion of thymic hormones that intervene in some steps of intra- and extra-thymic T cell differentiation. In the present paper, we studied the in vivo and in vitro influences of thyroid and steroid hormones on the secretion of thymulin, one of the chemically-defined thymic hormones. Triodothyronine injected in young mice or applied into supernatants of cultured thymic epithelial cells resulted in an increase of thymulin synthesis and secretion, respectively evaluated by the analyses of thymulin containing cells and thymulin levels. The influence of steroids was investigated in vivo by steroid depletion (adrenalectomy and/or castration) and in vitro by the addition of various steroids and/or their specific antagonists to cultured thymic epithelial cells. Surgical ablation of adrenals and/or gonads induced a transient depletion of circulating thymulin and, by feedback mechanism, an increase in the numbers of thymulin containing cells. From the in vitro data we could conclude that the various steroid hormones (that exhibited a stimulatory effect) can act directly on the thymic epithelium, probably via specific receptors. The bulk of data above described represents a strong evidence for the physiological involvement of the neuroendocrine network, on the hormonal function of the thymic epithelium.

Adrenal Cortex Hormones↗
PubMed2001

Evidence for a PTH-independent humoral mechanism in post-transplant hypophosphatemia and phosphaturia.

BACKGROUND: Patients undergoing successful kidney transplantation often manifest overt hypophosphatemia associated with exaggerated phosphaturia during the early post-transplant period (2 weeks to 3 months). The mechanism for this phenomenon has not been fully elucidated. We tested the hypothesis that a circulating serum factor [non-parathyroid hormone (non-PTH)], which operates during chronic renal failure (CRF) to maintain phosphate (Pi) homeostasis, can increase fractional excretion of Pi (FE(PO4)) in normal functioning kidney grafts during the early post-transplant period, thereby causing phosphaturia and hypophosphatemia. METHODS: Five groups of patients were studied: control subjects (group 1, N = 16), "early" (2 weeks to 1 month) post-transplant patients (group 2, N = 22), "late" (9 to 12 months) post-transplant patients (group 3, N = 14), patients with advanced CRF (glomerular filtration rate = 30 to 40 mL/min; group 4, N = 8), and patients who suffered from end-stage renal failure and were treated by chronic hemodialysis (group 5, N = 14). Group 2 manifested significant hypophosphatemia and phosphaturia when compared with groups 1 and 3 (Pi = 0.9 +/- 0.003 mg/dL, FE(PO4) = 68+/- 5%, P < 0.0005 vs. groups 1 and 3). Sera were taken from each of the five subject groups and applied to the proximal tubular opossum kidney (OK) cells. The activity of Na/Pi-type 4 (that is, OK-specific type II transporter) was evaluated by measuring Na(+)-dependent (32)Pi flux. The expression of Na/Pi type II mRNA and the abundance of Na/Pi protein were determined by Northern and Western blot assays, respectively. RESULTS: When compared with sera from groups 1 and 3, 10% sera taken from groups 2, 4, and 5 (incubated overnight with OK cells) inhibited (32)Pi flux by 25 to 30% (P < 0.0003). Both Na/Pi mRNA and the expression of Na/Pi protein were markedly augmented under the same conditions (P < 0.05 groups 2, 4, and 5 vs. groups 1 and 3). Time-course analysis revealed that the up-regulation of Na/Pi protein by sera from groups 2, 4, and 5 was observed as early as four hours of incubation, whereas augmented abundance of Na/Pi mRNA was only seen after eight hours of incubation. The addition of PTH (1-34) to sera from groups 2, 4, and 5 abolished the augmented expression of NaPi protein. We labeled OK cell surface membrane proteins with N-hydroxysuccinimide bound to biotin (NHS-SS-biotin). Biotinylated transporters incubated with the different sera were precipitated by strepavidin and identified by Western blot analysis. Cells incubated in sera from group 2 showed increased membrane bound transporter when compared with control sera, whereas the intracellular pool of the transporter was comparable between the two groups. CONCLUSION: A non-PTH circulating serum factor (possibly phosphatonin) that increases FE(PO4) during CRF is also responsible for phosphaturia and hypophosphatemia in the early period following successful kidney transplantation. The putative factor inactivates Na/Pi activity along with inhibition of the transporter trafficking from the cell membrane into the cytosol.

Adult↗
PubMed1994

In vitro lymphocyte-differentiating effects of thymulin (Zn-FTS) on lymphocyte subpopulations of severely malnourished children.

This work investigates how thymic dysfunction contributes to the depression of cell-mediated immunity in protein-energy malnutrition (PEM). In Bolivian children hospitalized for severe PEM, the size of the thymus was measured by echography, and the lymphocyte subpopulations were detected by using monoclonal antibodies. These data were compared with those obtained from healthy control subjects. Regardless of the clinical form of PEM, our results show a high degree of T lymphocyte immaturity in severely malnourished children, which correlates with a severe involution of the thymus. Before in vitro incubation with thymulin, this significant increase in the percentage of circulating immature T lymphocytes was concomitant with a decrease in mature T lymphocytes and a slight increase in cytotoxic T subpopulations. After in vitro incubation with thymulin, immature T lymphocytes decreased and mature T lymphocytes increased.

Anthropometry↗