PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Thymic Factor, Circulating”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1995

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.

Administration, Oral↗
PubMed1995

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.

Aging↗
PubMedDate not supplied

Histones and related preparations interfere with immunoassays for peptide hormones.

We report here that histones and certain related preparations generate a consistent interference with radioimmuno (RIA), immunoradiometric (IRMA), and enzyme-linked immunosorbent (ELISA) assays for a number of peptide hormones. Histones H1, H2A, H2B, H3, HIIA, HIIS, protamine, and the related preparations homeostatic thymus hormone and peptide MB35 generated a dose-dependent signal in both the human corticotropin-releasing hormone (CRH) and the human adrenocorticotropic hormone (ACTH) IRMA. This signal was not affected when the linker antiserum was removed from the IRMA reagent mixture, thus proving that the signal was not due to cross-reaction or sample contamination with CRH or ACTH. The above histone preparations, as well as protamine, but not ubiquitin, also generated a strong negative interference with RIAs for ACTH, CRH, rat growth hormone (rGH), and rat prolactin (rPRL). In an ELISA system for the thymic peptide facteur thymique sérique, histones and protamine again showed a strong interfering activity. When known amounts of rGH, rPRL, and hACTH were dissolved in charcoal-washed horse serum or supernatants from rat liver homogenates (centrifuged 1 h at 10,000 x g), and the corresponding RIAs and IRMA (for ACTH) were performed in the absence or presence of histones HIIA and HIIS (at 1 mg/ml level), an interfering activity of histones was again observed. We conclude that histones and some related peptide preparations have, when present in biologic fluids, a significant capacity to interfere with peptide immunoassays.

Adrenocorticotropic Hormone↗
PubMed1984

Studies on the zinc binding site to the serum thymic factor.

Gel filtration studies of 65Zn2+ binding to thymulin show that the nonapeptide can strongly bind one zinc metal ion. At pH 7.5, thymulin binds one zinc ion with an apparent affinity constant Kd of 5 +/- 2 X 10(-7) M. Binding is pH dependent. No binding is observed below pH 6.0. Ga3+, Al3+, Mn2+ and Cu2+ can compete with the binding of Zn2+ at pH 7.5. A good correlation between the competition potencies of metal ions used and the extent of biological activity of thymulin in the presence of these metal ions in an in vitro rosette assay is observed. Structural analogs of thymulin and non-thymulin-related peptides were used in a gel filtration technique to tentatively define the nature of amino acids present in the Zn2+-binding site of thymulin.

Binding Sites↗
PubMed1994

Protective effects of serum thymic factor to Leptospira interrogans serovar Copenhageni infection in Mongolian gerbils.

The susceptibility to Leptospira interrogans serovar copenhageni in Mongolian gerbils treated with 10 micrograms of serum thymic factor (FTS) 1 day before infection was examined. Susceptibility of gerbils treated 5 times with 10 micrograms of FTS was also investigated. Mortality of FTS-treated gerbils was significantly lower than that of controls when small challenge doses were used. To analyse the FTS-induced resistance to leptospiral infection, natural killer (NK) cell activity and macrophage activity were studied. Macrophage activity was unaltered but NK cell activity was enhanced in FTS-treated gerbils, with or without leptospiral infection. Since no side-effects of FTS were observed, this compound should be considered for the treatment of leptospirosis.

Animals↗
PubMed1989

Central administration of immunomodulatory factors alters neural activity and adrenocortical secretion.

This study was designed to examine the effects of intracerebroventricular administration of a variety of immunomodulatory factors upon cortical EEG, preoptic area/anterior hypothalamic (POA/AH) multiunit activity (MUA), and corticosterone secretion in conscious, freely moving rats. The substances tested were alpha-interferon (alpha-INF), thymic humoral factor (THF), histamine, and interleukin-1 (IL-1). Saline administration did not alter POA/AH MUA up to 45 min after injection but increased the total time and duration of synchronized EEG periods. alpha-INF and THF were found to significantly reduce POA/AH MUA and increased the amount and duration of synchronized EEG while decreasing basal plasma corticosterone levels. Histamine and IL-1 did not alter POA/AH MUA discharge but decreased EEG synchronization and evoked an increase in plasma corticosterone levels. These results demonstrate that some secretions of the immune system are able to alter EEG discharge and neural activity in an area of the brain known to modulate both immune and neuroendocrine secretory activity. The results also appear to be related to adrenocortical secretory activity, which was altered by the substances tested.

Adrenal Cortex↗
PubMed1992

In vivo effects of growth hormone on thymus function in aging mice.

It is well demonstrated that the normal functioning of the thymus gland is under neuroendocrine control. Thus, steroid, thyroid, and pituitary hormones can affect distinct structural and/or functional thymic parameters. Particularly growth hormone (GH) was shown to be capable of restoring some thymus functions in old individuals. This prompted us to carry out a multiparametric analysis of the thymus in young, middle-aged, and old mice, subjected to GH treatment lasting 3 or 6 weeks. For that, we treated animals with daily injections of ovine GH (2 micrograms/g BW). Although the general microarchitecture of the thymus remained unchanged following in vivo GH treatment, there was a clearcut increase in thymulin production, independent of the age group analyzed. Regarding the lymphoid compartment, we could not find evidence of changes in total thymocyte numbers nor in the subsets phenotypically defined by the expression of CD3, CD4, and CD8 antigens. Nonetheless, in GH-treated middle-aged and old mice, the concanavalin A-dependent proliferative response of thymocytes, as well as IL-6 production were enhanced compared to age-matched controls. These findings support the notion that GH has a pleiotropic effect upon the thymus, functionally affecting both microenvironmental and lymphoid compartments of the organ.

Aging↗
PubMed1992

Thymulin and its role in immunomodulation.

Even though thymulin was isolated, sequenced and characterised some 20 years ago and later identified as a thymic hormone involved in immunomodulation, much more work is still required to further understanding of the mechanisms of action(s) of this peptide. Since the observation, by a semiquantitative bioassay, of diminished levels of thymulin in immunodeficiency and autoimmune disease, new data obtained by radioimmunoassay have not only confirmed previous observations but also demonstrated that thymulin plays a role in the interaction between the immune system and the neuro-endocrine system. In this paper we give an up to date account of recent developments in research into the role of thymulin in immunomodulation.

Amino Acid Sequence↗
PubMed2003

Suppressor mechanism of serum thymic factor on tumor necrosis factor-alpha-induced apoptosis in the mouse pancreatic beta-cell line.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine considered to play a key role in beta-cell destruction in insulin-dependent diabetes mellitus (IDDM). Serum thymic factor (Facteur thymique serique; FTS) is a nonapeptide thymus hormone known to inhibit IDDM in a mouse model. In this study, the effect of TNF-alpha on the murine pancreatic beta-cell line MIN6 was examined. Cell shrinkage and detachment were seen in cells treated with 0-50 ng/ml TNF-alpha for 12h. Oligonucleosomal DNA fragmentation was determined from non-adherent cells, indicating that the TNF-alpha-induced cell destruction was attributed to apoptosis. Fragmented DNA was quantified by enzyme-linked immunosorbent assay to measure the amount of histone-bound oligonucleosomes. FTS was treated with TNF-alpha and the percentage of fragmented DNA was analyzed. The data indicate a distinct reduction of fragmented DNA at a concentration of 1 ng/ml FTS. Expression of TNF receptor I, inducible form of nitric oxide synthase (iNOS), interleukin-1 beta-converting enzyme (ICE), Bcl-2, and nuclear factor kappa B (NF-kappa B) was analyzed by reverse transcriptase-polymerase chain reaction to investigate the suppressor mechanism of FTS on TNF-alpha-induced apoptosis. FTS treatment suppressed the expression of iNOS and Bcl-2 mRNA in TNF-alpha-treated cells. The expression of NF-kappa B mRNA in TNF-alpha-treated cells was enhanced after FTS treatment, while that of ICE mRNA did not change in TNF-alpha-treated cells with or without FTS treatment. These results suggest that the inhibition of MIN6 cell death by FTS on TNF-alpha-induced apoptosis is caused by a negative feedback mechanism involving the inhibition of iNOS induction.

Animals↗
PubMed2005

Serum thymic factor, FTS, attenuates cisplatin nephrotoxicity by suppressing cisplatin-induced ERK activation.

Serum thymic factor (FTS), a thymic peptide hormone, has been reported to attenuate the bleomycin-induced pulmonary injury and also experimental pancreatitis and diabetes. In the present study, we investigated the effect of FTS on cis-diamminedichloroplatinum II (cisplatin)-induced nephrotoxicity. We have already demonstrated that cephaloridine, a nephrotoxic antibiotic, leads to extracellular signal-regulated protein kinase (ERK) activation in the rat kidney, which probably contributes to cephaloridine-induced renal dysfunction. The aim of this study was to examine the effect of cisplatin on ERK activation in the rat kidney and also the effect of FTS on cisplatin-induced nephrotoxicity in rats. In vitro treatment of LLC-PK1 cells with FTS significantly ameliorated cisplatin-induced cell injury. Treatment of rats with intravenous cisplatin for 3 days markedly induced renal dysfunction and increased platinum contents in the kidney cortex. An increase in pERK was detected in the nuclear fraction prepared from the rat kidney cortex from days 1 to 3 after injection of cisplatin. FTS suppressed cisplatin-induced renal dysfunction and ERK activation in the kidney. FTS did not influence any Pt contents in the kidney after cisplatin administration. FTS has been shown to enhance the in vivo expression of heat shock protein (HSP) 70 in the kidney cortex. The beneficial role of FTS against cisplatin nephrotoxicity may be mediated in part by HSP70, as suggested by its up-regulation in the kidney cortex treated with FTS alone. Our results suggest that FTS participates in protection from cisplatin-induced nephrotoxicity by suppressing ERK activation caused by cisplatin.

Animals↗
PubMed2006

Peripheral and mesencephalic transfer of a synthetic gene for the thymic peptide thymulin.

Thymulin is a thymic peptide with antiinflammatory activity in the brain. We constructed a recombinant adenoviral vector, RAd-FTS, expressing a synthetic DNA sequence encoding met-FTS, a biologically active analog of thymulin and used it for peripheral and central gene transfer in rats. Thymulin concentration in serum and brain tissue was determined by bioassay. Reporter gene expression in the substantia nigra (SN) was quantitated by enzymohistochemistry or fluorescence microscopy using an appropriate image analysis software. A single intramuscular injection (10(8) plaque forming units (pfu)/animal) of RAd-FTS in thymectomized rats (nondetectable serum thymulin) induced supraphysiologic serum thymulin levels for at least 110 days (123+/-22 fg/ml versus 598+/-144 fg/ml in intact and vector-injected rats, respectively). Stereotaxic intranigral injection of RAd-FTS induced steady expression levels of met-FTS for at least 90 days, whereas expression of adenovirally transferred reporter genes coding for green fluorescent protein fused to HSV thymidine kinase (GFP-TK)(fus) or E.coli beta-galactosidase (beta-gal), declined drastically within a month (% transgene expression in the SN on post-injection day 30 relative to day 2 was: 18, <1 and 125%, for beta-gal, (GFP-TK)(fus) and met-FTS, respectively). We conclude that RAd-FTS constitutes a suitable biotechnological tool for the assessment of peripheral and central thymulin gene therapy in animal models of nigral dopaminergic neurodegeneration induced by pro-inflammatory agents.

Adenoviridae↗
PubMed2005

In vitro and in vivo effects of mercuric chloride on thymic endocrine activity, NK and NKT cell cytotoxicity, cytokine profiles (IL-2, IFN-gamma, IL-6): role of the nitric oxide-L-arginine pathway.

Mercury (Hg2+) affects cell-mediated immunity, including thymulin production. Thymulin, a zinc-dependent thymic hormone synthesized by thymic epithelial cells (TECs), is involved in NK cell cytotoxicity and Th1 cytokine production (IL-2 and IFN-gamma), which in turn affect both NKT and classic NK spleen cell cytotoxicity. High doses of Hg2+ induce an inflammatory status, increased production of IL-6 and consequent Th1/Th2 imbalance as well as cell-mediated immune depression. The mechanisms by which Hg+ affects the cell-mediated immune response are still unclear. The nitric oxide (NO) pathway may be implicated. The aim of this work was to further explore its noxious role in innate and adaptive immunity and to study the possible role played by the NO pathway. Young Balb/c mice treated in vivo for 1 month with 1.0 mg HgCl2/kg b.w. showed low thymulin activity, depressed NO production (as measured by nitrite and nitrate plasma levels), impaired classic NK spleen cell cytotoxicity, decreased Th1 (IL-2 and IFN-gamma) cytokine profiles, and increased IL-6 production. In vitro, 10(-6) M of HgCl2 inhibited active thymulin kinetics, TEC proliferation, NKT cell cytotoxicity and Th1 cytokine production, whereas IL-6 increased. L-arginine restored thymulin activity, TEC proliferation, NKT cytotoxicity, cytokine profiles and nitrite and nitrate plasma levels both in vivo and in vitro. Since L-arginine is the substrate for NO production, it may compensate for the cell-mediated immune defect induced by HgCl2, via the arginine-NO-pathway. L-arginine is also able to reduce glomerular kidney IgG antibodies deposits induced by higher dose of HgCl2 administration.

Animals↗
PubMed2005

The role of nicotinic acetylcholine receptors in lymphocyte development.

The sizes of lymphocyte populations in lymphoid organs of nicotinic acetylcholine receptor knockout and chimera (knockout/wild-type) mice were studied by flow cytometry. The absence of beta2 subunit decreased, while nicotine treatment increased B lymphocyte numbers in the bone marrow. In chimera mice, either beta2 or alpha7 subunits influenced lymphocyte populations in primary lymphoid organs, while in the spleen, only alpha7 receptors were critical. More annexin V-positive B cells were found in the bone marrow of knockout than wild-type animals. We conclude that nicotinic receptors are involved in regulating lymphocyte development and control the B lymphocyte survival.

Animals↗
PubMed2006

Altered expression of Th1-type chemokine receptor CXCR3 on CD4+ T cells in myasthenia gravis patients.

The expression of chemokine receptors on peripheral blood lymphocytes and thymocytes of myasthenia gravis (MG) patients was analyzed before and after therapy with special reference to the thymic histopathology. Before therapy, MG patients showed reduced frequency of CD4+ T cells expressing T-helper1 (Th1) type chemokine receptor CXCR3, with a significantly lower frequency in the thymoma group than in the thymic hyperplasia group, while the frequencies of CXCR3-positive CD8+ T cells remained normal irrespective of the thymic pathology. Both CD4+ cells and CD8+ cells of the hyperplasia group showed significantly increased expression of CCR1 on the cells followed by a reduction to the control level after therapy. No significant changes in the frequencies of CCR2, CCR3, CCR4, and CCR5 were observed in either MG group. There was a significant inverse correlation between the percentage of CXCR3-positive CD4+ T cells and the disease severity assessed with the MGFA scale (Fig. 1, r=-0.55, p=0.0047). The CXCR3 expression on CD4+ cells was increased toward the control level long after the initiation of therapy. The thymomas showed significantly higher percentages of CXCR3-positive CD4+CD8- single positive cells than the control thymuses and, though not significantly, the hyperplastic thymuses also showed higher percentages. These results indicated that Th1-type chemokine signalings were altered in the MG patients, particularly those with thymoma, and that the thymus and thymoma are important sites of Th1-type reactions. The slow clinical improvement of MG symptoms after treatment may be explained partly by the gradual normalization of CXCR3-mediated signaling.

Adult↗
PubMed2004

Effects of thymulin and GnRH on the release of gonadotropins by in vitro pituitary cells obtained from rats in each day of estrous cycle.

The effects of thymulin and GnRH on FSH and LH release were studied in suspension cultures of anterior pituitary cells from female adult rats sacrificed on each day of the estrous cycle. The spontaneous release of gonadotropins by pituitaries, as well as their response to GnRH or thymulin addition, fluctuated during the estrous cycle. Adding thymulin to pituitary cells from rats in diestrus 1 increased the concentration of FSH; while in cells from rats in estrus, FSH level decreased. Thymulin had a stimulatory effect on the basal concentration of LH during most days of the estrous cycle. Adding GnRH increased FSH release in cells from rats in diestrus 1, diestrus 2, or proestrus, and resulted in higher LH levels in cells obtained from rats in all days of the estrous cycle. Compared to the GnRH treatment, the simultaneous addition of thymulin and GnRH to cells from rats in diestrus 1, diestrus 2, or proestrus resulted in lower FSH concentrations. Similar results were observed in the LH release by cells from rats in diestrus 1, while in cells from rats in proestrus or estrus, LH concentrations increased. A directly proportional relation between progesterone serum levels and the effects of thymulin on FSH release was observed. These data suggest that thymulin plays a dual role in the release of gonadotropins, and that its effects depend on the hormonal status of the donor's pituitary.

Animals↗