Effect Of Thymic Hormone Research Articles

Effects of thymic hormone on reactive oxygen species-scavengers and renal function in tacrolimus-induced nephrotoxicity

The effects of a thymic hormone (Facteur thymique serique; FTS) on renal reactive oxygen species-scavenging enzymes or substances in heminephrectomized rats with and without tacrolimus-induced nephrotoxicity were studied. Rats received both oral dose of tacrolimus (5 mg/kg/day) and subcutaneous administration of three dosages of FTS (5, 50, and 250 μg/kg/day) over 28 days (Group A). In Group B, they received three dosages of FTS alone (0.5, 5, and 50 μg/kg/day) or FTS 50 μg/kg/day with tacrolimus over 28 days. Each dose of FTS (Group A) partially elevated renal creatinine clearances. Tacrolimus enhanced renal glutathione reductase (GSH-R) activities and glutathione (GSH) and depressed catalase (CAT) activities. FTS increased GSH levels and GSH-R activities. Although FTS alone did not change CAT activities, CAT activities recovered as a result of concomitant use of FTS (Groups A and B). A significant positive correlation was found between CAT activity and creatinine clearance. These findings suggest that FTS is useful for the prevention of tacrolimus-induced nephrotoxicity, and that the increase of renal CAT activity in the defense mechanism of FTS might be important for cell protection against active oxygen species.

Immunopotentiating and Immunotherapeutic Effects of Thymic Hormones and Factors with Special Emphasis on Thymic Humoral Factor THF-γ2

The essential role played by the thymus in the development of the immune response was well documented in many publications. These findings prompted a long series of studies devised to define the factors produced and secreted by thymus cells, which are involved in the development and nature of immunological responsiveness. First experiments done with crude thymus extracts were followed by isolation of purified products and finally by chemical characterization and synthesis of immunologically active thymus-derived peptides. In this article we review the various thymic hormones and factors described, that is, thymosin fractions 5, the thymosins, prothymosin alpha, thymulin (FTS-Zn), thymopoietin, thymostimulin (TP-1), Thymic humoral factor (THF), and THF-gamma2. Studies demonstrating the activity of the various thymic factors in increasing the immunocompetence potential in both in vitro and in vivo conditions are discussed. The immunostimulatory potential of thymic factors was also investigated in experimental models where beneficial therapeutic effects were sought in a situation of immunological malfunction. The last part of the review is dedicated to clinical trials with thymic factors that revealed improvement in the immunocompetence potential in cases of immunodeficiencies, viral infections, and cancer and its correlation with therapeutic effectiveness. It seems that more research is required in order to better define conditions for the use of thymic factors in immunotherapy.

Effect of thymic hormones on induction of experimental allergic encephalomyelitis in old mice.

This study was aimed at restoring decreased T-cell functions and reduced susceptibility to proteolipid apoprotein (PLP) induced-experimental allergic encephalomyelitis (EAE) in old mice with thymic hormones. Thymosin fraction 5 (TF-5) and serum thymic factor (FTS) had no significant in vitro and in vivo effect on proliferative responses to PLP and concanavalin A (Con A), and on EAE induction in young and old mice. These results suggest that decreased T-cell functions cannot be restored by these thymic hormones tested.

Thymic Peptides as Anti-Aging Drugs: Effect of Thymic Hormones on Immunity and Life Span

(1990). Thymic Peptides as Anti-Aging Drugs: Effect of Thymic Hormones on Immunity and Life Span. International Journal of Neuroscience: Vol. 51, No. 3-4, pp. 371-372.

Effect of thymic hormones on interleukin 2 synthesis by lymphocytes from HIV-positive pre-AIDS subjects.

The PHA-induced synthesis of interleukin 2 (IL-2) by peripheral blood lymphocytes (PBL) from 9 normal and 8 pre-AIDS individuals was evaluated. IL-2 content in supernatant fluids of PBL cultures derived from pre-AIDS patients was only around 20% of that found in normal PBL cultures. The addition of two thymic preparations, thymosin faction 5 and TFX-Polfa, to PHA-stimulated PBL cultures from pre-AIDS patients caused significant increase of IL-2 content in cultures. Thymosin alfa 1 was ineffective in this respect. However, thymic factors corrected only partially the defective IL-2 synthesis by PBL from pre-AIDS patients increasing it to ca. 35% of value for normal PBL. The findings suggest the potential of PBL from pre-AIDS patients to respond in vitro to enhancing activity of thymic hormones.

Thymic hormones in radiation-induced immunodeficiency: I. Induction of mature interleukin 1 responsive cell in the thymus by thymosin fraction 5

The restorative effect of thymosin fraction 5 (TF5) on the thymus of γ-irradiated mice was examined. Four different mouse strains were used in this study since earlier work determined that the degree of response to TF5 is strain dependent. The responsiveness to comitogenic effect of interleukin 1 (IL-1) was used to measure the rate of recovery of immunocompetent cells in the thymus, since only more mature PNA −, Lyt-1 +-2 − medullary cells respond to this monokine. Contrary to several earlier reports that radioresistant cells repopulating the thymus within the first 10 days after irradiation are mature, corticosteroid resistant, immunocompetent cells, the thymic cells from irradiated mice in all strains used had greatly reduced responses to IL-1. Daily intraperitoneal injections of TF5 increased significantly the responses of thymic cells to IL-1 in 10- to 13-weeks-old C57Bl/KsJ, C57B1/6, C3H/HeJ, and DBA/1 mice. Older mice, 5 months or more in age, of DBA/1 strain did not respond to treatment with TF5. However, C3H/HeJ mice of the same age were highly responsive. In conclusion, (1) cells repopulating the thymus within 12 days after irradiation contain lower than normal fraction of mature IL-1 responsive cells, (2) thymic hormones increase the rate of recovery of immunocompetent cells in the thymus, and (3) the effect of thymic hormones is strain and age dependent.

Effects of thymic hormones on intracellular cAMP and on PGE 2release in murine thymic subpopulations

Effects of thymic hormones on intracellular cAMP and on PGE 2release in murine thymic subpopulations

4 Effect of Thymic Hormones on Human Lymphocytes

Several peptides have been isolated from thymic tissues and found to circulate in peripheral blood, establishing the role of the thymus as an endocrine gland. These peptides possess the ability to induce differentiation of T cell precursors into more mature T lymphocytes. Evidence of maturation was established by the demonstration of appearance of T cell surface markers (HTLA, E rosette receptors, T cell antigen detected by the monoclonal antibody anti-Leu-2a) on marrow or peripheral blood cells that did not bear these markers originally. On the other hand, PNA receptors and enzymatic activity of TdT were lost after incubation of immature T cell populations with such peptides. Marked enhancement of T cell functions, demonstrated by responses to phytomitogens or allogeneic cells in MLR, was also observed after exposure to thymic peptides. Thus, as T cell precursors differentiate into T lymphocytes, they lose their markers of immaturity and acquire the surface phenotype and the functional activities characteristic of mature peripheral T cells. Acquisition of T cell specificities by marrow cells were shown to require RNA and protein synthesis. In contrast to marrow precursors, the majority of inducible PBLs were not affected by RNA or protein synthesis inhibitors. Less than one per cent of them were found to require protein synthesis. These findings indicate that T cell precursors in marrow are at an earlier stage of differentiation than those in peripheral blood. Evaluation of T cell differentiation in patients with immunodeficiency diseases and leukaemia revealed marked heterogeneity in the response of their marrow or peripheral blood cells in vitro to thymic extracts, peptides or thymic epithelium. In patients with SCID, abnormalities ranging from a complete absence of definable T cell precursors to partial differentiation resulting in the acquisition of the HTLA, or HTLA and E rosette markers were observed. In no case could significant responses to mitogens be elicited. However, following successful transplantation of fetal liver plus thymus, or of bone marrow from HLA-matched sibling donors, marrow cells from these patients acquired the full range of thymic hormone-inducible characteristics. In contrast to SCID patients, those with the DiGeorge syndrome, ataxia telangiectasia, CVI or Wiskott—Aldrich syndrome were found to possess T cell precursors that could respond to thymic hormones in vitro. Furthermore, the study of marrow cells from immunodeficient patients revealed several stages of T lymphocyte differentiation. Cells developing the HTLA phenotype are believed to be the precursors of those that acquire the E rosette receptors, and the latter can differentiate into cells responding to the phytomitogens conA or PHA, or to alloantigens. Similar investigations in vitro were performed before and after treatment of patients with thymic hormones. The results suggest that expression of T cell surface markers as well as functions, such as help, suppression or NK activity, can be induced in vivo. In conclusion, based upon the accumulation of data obtained in vitro on normal and pathological materials, it seems likely that thymic hormones can provide some of the signals necessary for T lymphocyte maturation and should, therefore, have therapeutic application in the future.

9 Effects of Thymic Hormones on Immunodeficiency

9 Effects of Thymic Hormones on Immunodeficiency

B and T lymphocytes in lymphoproliferative diseases of the skin. Effect of a thymic hormone on the immunocompetence of T lymphocytes.

Cell-mediated immunity using the E-rosette technique, the graft-versus-host reaction and intradermal skin tests were investigated in two groups of patients, twenty-two with benign lymphoproliferative diseases of the skin (lymphocytic infiltration of the skin and lymphadenosis benigna cutis) and nine with malignant lymphoproliferative diseases (mycosis fungoides and lymphoma cutis). The effect of thymic hormone upon T lymphocytes which proved to have impaired functional capacity was investigated. Seventeen of the twenty-two patients with benign lymphoproliferative diseases were found to have intact cellular immunity whereas seven of the nine patients with malignant disease proved to be immunodeficient. The determination of immune competence may be of help in establishing the correct diagnosis in doubtful cases and might also be useful in the follow-up of these patients. The improvement in functional capacity of T lymphocytes resulting from their interaction with a thymic hormone indicates that it holds therapeutic promise.