thymic-factor--circulating and Immunologic-Deficiency-Syndromes

Topics: Aging; Animals; Disease Models, Animal; Dwarfism, Pituitary; Humans; Immune System; Immunologic Deficiency Syndromes; Mice; Mice, Mutant Strains; Neurosecretory Systems; Rejuvenation; Thymectomy; Thymic Factor, Circulating; Thymus Gland; Thyroxine

The manuscript will provide an in-depth and critical review of the nomenclature, biochemistry, biological properties, and a summary of published and on-going clinical trials with all reported thymic preparations, including both partially purified thymic factors (e.g., thymosin fraction 5, thymostimulin) as well as purified and synthesized thymic peptides (e.g., thymosin alpha 1, thymulin). Particular emphasis will be placed on which thymic peptides should be categorized as true hormones. In addition, the comparative biochemistry and biological activity in animals will be summarized and contrasted for all the currently available thymic factors. The effects, in vitro of thymic factors, on peripheral blood lymphocytes isolated from normal donors and patients with primary immunodeficiency disorders, autoimmune disorders, and neoplastic disorders will also be reviewed. Finally, a detailed critical summary of the clinical trials performed with each of the thymic preparations will be presented with an emphasis on treatment of patients with cancer.

Topics: Amino Acid Sequence; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Autoimmune Diseases; Biological Assay; Cell Differentiation; Epithelium; Humans; Immunologic Deficiency Syndromes; Immunotherapy; Neoplasms; T-Lymphocytes; Terminology as Topic; Thymectomy; Thymic Factor, Circulating; Thymopoietins; Thymosin; Thymus Extracts; Thymus Gland; Thymus Hormones

Recent immunological research has concentrated on the complex and subtle interactions between T cells, B cells and accessory cells. In these studies, little attention has been given to the adult thymus gland. Modern textbooks of disease and anatomy all stress that the gland undergoes fatty involution with age in man but omit reference to the statements here and there in the literature that the gland is active and produces lymphocytes throughout life. To suggest that the bone marrow, which also builds up fat throughout life, is atrophic and not important to adult man would deny all modern hematological concepts. Yet few people today take a parallel view of the thymus except perhaps those investigating aging and thymic hormones. In both of these areas of research it is obvious that the thymus must be active throughout life for continued good health. This brief review urges that a thorough understanding of the vital importance of the thymus in adult life is now needed. From it could emerge a new philosophy on the treatment of immune diseases in both the young (SCID and AIDS patients) and in the aged (autoimmune conditions and cancers) and it would aid our treatment of patients recovering from illness and from many drug treatments.

Topics: Acquired Immunodeficiency Syndrome; Aging; Animals; Cell Cycle; Cell Movement; DiGeorge Syndrome; Hematopoiesis; Humans; Immunologic Deficiency Syndromes; Organ Size; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland; Thymus Hormones; Time Factors

The epithelial cells of the thymus synthesize at least 30 different polypeptides: the thymic hormones. The structure of 4 of them is well known. They are named thymosin alpha 1, thymopoietin, thymulin and thymic humoral factor. Biological functions and secretion regulation of thymic hormones are described as well as the interactions between brain, thymus and endocrine glands. Blood levels and clinical usefulness of thymic hormones are reviewed in different congenital or acquired immunodeficient states and in autoimmune diseases.

Topics: Acquired Immunodeficiency Syndrome; Autoimmune Diseases; Humans; Immunologic Deficiency Syndromes; Peptide Fragments; Thymalfasin; Thymic Factor, Circulating; Thymopentin; Thymopoietins; Thymosin; Thymus Extracts; Thymus Hormones

Topics: Adult; Aged; Animals; Antibody-Producing Cells; Cell Membrane; Child; Female; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Lymphocyte Activation; Lymphopenia; Maternal-Fetal Exchange; Mice; Mice, Inbred Strains; Nutrition Disorders; Pregnancy; T-Lymphocytes, Cytotoxic; Thymic Factor, Circulating; Zinc

Topics: Animals; Autoimmune Diseases; Growth Inhibitors; Humans; Immunity; Immunologic Deficiency Syndromes; Interferons; Interleukin-1; Interleukin-2; Lymphotoxin-alpha; Neoplasms; Thymic Factor, Circulating; Thymosin; Thymus Hormones; Transfer Factor

Clinicoimmunological examination of children to be BCG revaccinated showed 50% of them to have immunodeficiency. Primarily T-cell and macrophagal components of immunity were compromised. The study of immune response to BCG in animals with T-cell and macrophage immunodeficiency validated feasibility of improving antituberculous vaccination efficacy by using thymalin and sodium nucleinate.

Topics: Adjuvants, Immunologic; Adolescent; Animals; BCG Vaccine; Child; Drug Evaluation, Preclinical; Humans; Immunity, Cellular; Immunization, Secondary; Immunologic Deficiency Syndromes; Mice; Nucleic Acids; Thymus Hormones; Tuberculin Test; Tuberculosis, Pulmonary; Ukraine; Urban Population

The authors investigated spontaneous and induced secretion of cytokins at different stages of generalized tuberculosis. In the development of infection there were inhibited IL-2 synthesis in response to ConA, emerging activity of PNO-alpha in response to the inductors in blood serum and culture of peritoneal macrophages, enhanced secretion of IL-6. Complete immunodeficiency was associated with cessation of IL-2 synthesis by splenocytes, elevated production of IL-6 by peritoneal macrophages, low concentrations of PNO-alpha in the serum and peritoneal macrophage cultures. In the treatment of M. bovis-infected mice with antibacterial drugs alone IL-6 secretion by peritoneal macrophages and PNO-alpha activity in the serum were increased. Immunocorrection resulted in marked activation of IL-2 production by splenocytes in response to ConA as well as enhanced synthesis of IL-6 in unstimulated cultures of peritoneal macrophages.

Topics: Adjuvants, Immunologic; Animals; Antitubercular Agents; Concanavalin A; Drug Evaluation, Preclinical; Drug Therapy, Combination; Immunity, Cellular; Immunologic Deficiency Syndromes; Interleukin-2; Interleukin-6; Isoniazid; Mice; Mycobacterium bovis; Rifampin; Thymus Hormones; Tuberculosis; Tumor Necrosis Factor-alpha

Topics: Adjuvants, Immunologic; Adult; Circadian Rhythm; Female; Humans; Hydrocortisone; Immunologic Deficiency Syndromes; Succinate Dehydrogenase; T-Lymphocytes; Thymus Hormones

Topics: Adjuvants, Immunologic; Adult; Aged; Blood; Combined Modality Therapy; Diabetes Complications; Diabetes Mellitus; Humans; Immunologic Deficiency Syndromes; Middle Aged; Prodigiozan; Thymus Hormones; Ultraviolet Therapy; Wound Infection

The immune status has been assessed in 73 patients with postabortal endometritis and thymalin and T-activin have been evaluated as an intervention for secondary immunodeficiency associated with this condition. These drugs were found to have immunomodulating effects on quantitative and qualitative characteristics of T- and B-lymphocytes and their subpopulations and on phagocytic function of polynuclears. Comprehensive therapy using thymalin and T-activin improves the efficacy of management of postabortal endometritis.

Topics: Abortion, Spontaneous; Adjuvants, Immunologic; Adolescent; Adult; Endometritis; Female; Humans; Immunity, Innate; Immunologic Deficiency Syndromes; Peptides; Pregnancy; Thymus Extracts; Thymus Hormones

Thymulin, a peptide secreted by human thymic epithelial cells, circulates in peripheral blood. Levels of plasma thymulin (FTS-Zn) activity were analyzed in 21 patients with lethal combined immunodeficiency disorders who were treated with transplantation of HLA-haplotype-mismatched parental bone marrow depleted of T cells by differential agglutination with soybean agglutinin and E-rosetting (SBA-E-BMT). Among these 21 infants, 15 were patients with severe combined immunodeficiency (SCID) and 6 had combined immunodeficiency (CID) with Omenn's syndrome or CID with T cell predominance (CIDTP). In contrast to normal infants who possess high levels of plasma thymulin activity, 20 of the 21 patients demonstrated undetectable or low plasma thymulin levels for their age at admission prior to transplantation. Following SBA-E-BMT, however, thymulin became detectable in the plasma of 17 of 18 evaluable patients and reached normal or near-normal levels between 21 and 125 days posttransplant. In patients in whom the timing of engraftment could be established by emergence of donor lymphocytes, thymulin appeared in the plasma at approximately the same time as lymphoid chimerism was detected, and in all patients who were engrafted and immunologically reconstituted, the increment in thymulin levels preceded development of immune functions. These studies support the concept that normal marrow-derived cells in the graft can provide a stimulus necessary for induction of thymic epithelial secretory function in patients with thymic dysplasia. Further, immunologic reconstitution in these patients was not seen following SBA-E-BMT unless and until recovery of thymus function had been observed.

Topics: Bone Marrow Transplantation; Chimera; Female; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Lymphocyte Depletion; Male; Phytohemagglutinins; Plant Lectins; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones

Eighteen non-institutionalized Down's syndrome (DS) children (mean age: 7.0 +/- 10/12 years) with a history of respiratory tract, auditory and skin infections, low plasma levels of a nonapeptide thymic hormone, i.e. Serum Thymic Factor (STF), high plasma levels of inactive zinc-unbound STF molecules, and reduced absolute number of circulating T-lymphocytes, were given an oral non-pharmacological supplementation of zinc sulphate (1 mg Zn++/kg body weight/day for 2 months; two cycles, 10 months apart) and monitored immunologically before and after each cycle. A dramatic increase of plasma STF level and concomitantly an almost complete disappearance of inactive STF molecules was observed after each cycle. The absolute number of circulating T-lymphocytes was significantly increased by zinc treatment. The marginal zinc deficiency was also corrected without any appreciable influence on copper plasma levels. A reduction of recurrent infections and an improvement in school attendance after zinc supplementation were recorded. These beneficial effects of zinc supplementation were also noted in those DS children who did not show an apparent zinc deficiency, as assessed by measuring zinc plasma level. The reduced number of circulating B lymphocytes and the impaired lymphocyte responsiveness to phytohaemagglutinin and concanavalin A were not restored. On the whole, these findings suggest that there exists a defect in the bio-availability and/or in the utilization of zinc in DS. This alteration, of unknown origin, can be underestimated on the simple basis of the zinc plasma level and can be corrected with moderate nutritional zinc supplementation.

Topics: Child; Copper; Down Syndrome; Female; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Male; Opportunistic Infections; Sulfates; Thymic Factor, Circulating; Thymus Hormones; Zinc; Zinc Sulfate

A Hispanic infant girl with DiGeorge syndrome underwent successful bone marrow transplantation (BMT) at age 28 1/2 weeks. She had typical facies, a cardiac defect, hypoparathyroidism, severe T and B cell immunodeficiency, and low levels of facteur thymique serique (FTS). In vitro incubation of the peripheral blood lymphocytes with thymosin alpha 1 showed no increase in the number of T cells on two occasions. A fetal thymus for transplantation was not available, and further review of past experience with thymic cells or factors revealed inconsistent and incomplete responses. Because of the patient's worsening clinical and immunologic status, BMT was performed, with her histocompatible brother as donor. The patient has had a good clinical and immunologic response to BMT, with evidence of T cell engraftment, improved B cell function, and increased levels of serum FTS. This experience indicates that minimal thymic influence is necessary for successful BMT and that patients with DiGeorge syndrome with significant T cell deficiency may benefit from this treatment.

Topics: Adult; Age Factors; B-Lymphocytes; Bone Marrow; Bone Marrow Transplantation; DiGeorge Syndrome; Evaluation Studies as Topic; Female; Humans; Immunoglobulin G; Immunologic Deficiency Syndromes; Infant, Newborn; Leukocyte Count; Male; T-Lymphocytes; Thymalfasin; Thymic Factor, Circulating; Thymosin

The work deals with the results of the study of T-lymphocytes and their subpopulations (active, thermostable, theophylline-sensitive and theophylline-resistant) in 102 children with chronic viral hepatitis B, depending on the effectiveness of thymalin therapy. The sensitization of lymphocytes to specific antigens was studied. Among patients with chronic viral hepatitis B and cirrhosis of the liver the homozygous phenotype of haptoglobin is registered essentially more frequently (63.6% and 82.4% respectively) than among healthy persons (44.0%). The patients of this group showed a decrease in the number of T-lymphocytes, disturbances in the suppressor/helper ratio: hypersuppression in persisting hepatitis and hyposuppression in active hepatitis. In 71.6% of cases thymalin therapy produced an effect manifested by clinico-biochemical remission, an increase in the number of T-lymphocytes, thermostable cells and the normalization of the T-suppressor/T-helper ratio. In these patients sensitization to HBsAg essentially decreased (from 30.5% to 13.9%), while sensitization to human liver lipoprotein retained its high level even after treatment with thymalin.

Topics: Adjuvants, Immunologic; Adolescent; Child; Child, Preschool; Chronic Disease; Haptoglobins; Hepatitis B; Hepatitis B Surface Antigens; Humans; Immunologic Deficiency Syndromes; Phenotype; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Thymus Hormones

Topics: Animals; Cattle; Cell Differentiation; Cell Division; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Lymphocyte Activation; Mice; Spleen; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland; Thymus Hormones

Thymus-dependent immunity as well as thymic factor and corticosteroid influence upon it were studied in 36 patients with disseminated sclerosis. The illness was diagnosed according to the Poser system with the help of the spontaneous erythrocyte rosette test. The sensitivity of T lymphocytes to thymaline, to basic myelin protein and to prednisolone was analyzed. The Soviet drug thymaline, obtained from calf thymus, was first used for the treatment of disseminated sclerosis. Clinical and immunological results turned out positive. The possibility of differential immunomodulating therapy of disseminated sclerosis is shown.

Topics: Adjuvants, Immunologic; Adult; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Prednisolone; Rosette Formation; T-Lymphocytes; Thymus Hormones

Normal individuals aged over 50 and most young Down's syndrome (DS) subjects had markedly reduced concentrations of circulating thymic hormone (facteur thymique sérique, FTS). Plasma from these two groups contained factors capable of inhibiting biological activity of FTS in vitro. Addition of zinc sulphate to plasma samples from DS subjects or the older individuals induced concentrations of FTS comparable to those observed in young healthy people and completely prevented FTS-inhibitory activity. These findings suggest that biologically active circulating thymic hormone is bound to zinc. The decline in thymic hormone activity in older individuals and DS subjects may be the result of changes in the mechanism of zinc-dependent activation of FTS molecules, which are probably associated with marginal zinc deficiency rather than with a primary failure of the thymus. Addition of zinc salt to plasma samples unmasks the presence of inactive FTS molecules.

Topics: Adolescent; Adult; Aged; Aging; Child; Child, Preschool; Down Syndrome; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Middle Aged; Molecular Weight; Sulfates; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland; Thymus Hormones; Zinc; Zinc Sulfate

Ninety-eight patients with different patterns of chronic nonspecific pulmonary diseases (CNPD) were examined for thymus-dependent immunity. The clinical manifestations of T lymphocyte dysfunction included a torpid recurrent inflammatory process in the respiratory system, respiratory viral infections, short-term efficacy of antibacterial drugs. The patients demonstrated a decrease in the number of T lymphocytes, in production of immune interferon, and in secretion of serum thymic humoral factor. Application of tactivin, a new immunomodulator, is an effective approach to correction of the disorders enumerated. The drug has a beneficial effect on inflammatory process, reduces the symptoms of virus-induced intoxication. Administration of repeated tactivin treatment made it possible to shorten the time of repeated tactivin treatment made it possible to shorten the time of staying at hospital, to reduce the frequency of CNPD relapses from 80 to 36% within the period from 2 months to 1.5 years. This permits recommending the drug during resistance to antibiotic therapy.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Chronic Disease; Combined Modality Therapy; Drug Evaluation; Female; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Interferon Type I; Leukocyte Count; Lung Diseases; Lymphocyte Activation; Male; Middle Aged; Peptides; T-Lymphocytes; Thymic Factor, Circulating; Thymus Extracts

Topics: Abnormalities, Multiple; Adjuvants, Immunologic; Adolescent; Branchial Region; Child; Facial Asymmetry; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Jaw Abnormalities; Syndrome; Thymus Hormones

Twenty-three patients with severe combined immunodeficiency disease were studied for circulating thymic hormone levels (facteur thymique serique, FTS), 21 prior to treatment by transplantation of bone marrow, thymus or fetal liver. Thirteen showed undetectable FTS activity. Only two had normal levels of this hormone. In serial determinations of FTS activity prior to and after transplantation, patients given bone marrow transplants developed sustained increments of serum FTS activity early in the course of their immunological reconstitution. However, patients given transplants of fetal liver alone or fetal liver plus thymus from fetuses of less than 12 weeks gestation generally did not show an increment of FTS activity during the period of observation. Transplantation of irradiated thymus derived from fetuses of more than 14 weeks gestation produced sustained increases of thymic hormone activity. These observations suggest that a cell of haematopoietic origin provides a stimulus necessary for differentiation or maturation of thymic secretory activity and that this cell(s) is present in post-natal marrow, but is either undeveloped or immature in the early fetal liver or fails to migrate to the thymus of an allogeneic host.

Topics: Antibody Formation; Bone Marrow Transplantation; Child; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Liver Transplantation; Lymphocyte Activation; Rosette Formation; Thymic Factor, Circulating; Thymus Gland; Thymus Hormones; Time Factors

Lymphocytes from five children suffering from ataxia telangectasia or various unclassified immune deficiencies were tested in vitro for their sensitivity to synthetic serum thymic factor (FTS). The percentages of cells bearing T cell markers were elevated after incubation with FTS at graded concentrations (0.25, 2.5 and 25 ng/ml), by microlymphocytotoxicity or indirect immunofluorescence, using monoclonal anti-Lyt1 antibodies. In four cases, more than 30% of the non-T non-B cells acquired the Lyt1 T cell marker. These four children had low levels of circulating FTS. In the fifth child, who had a normal serum FTS level, and in two age-matched controls, there was no significant increase in the percentage of cells bearing the T marker.

Topics: Adolescent; Antibodies, Monoclonal; Ataxia Telangiectasia; Child; Child, Preschool; Female; Fluorescent Antibody Technique; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Male; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones

The effects were studied of the degree of immunodeficiency produced by thymectomy of one-month-old rats on the course of experimental tuberculosis induced 3, 6 and 9 months after thymectomy. Subject to study was also the effect of immunodeficiency correction with thymalin on the tuberculous process. It was established that the lungs of thymectomized rats infected 9 months after the thymectomy were damaged more severely as compared with control or thymalin-treated animals. In thymectomized rats treated with thymalin, the absolute content of medium-sized and big lymphocytes in peripheral blood was found to be lower, the content of small lymphocytes being unchanged throughout all observation periods. The time course of migration activity (spontaneous and in response to PPD) in rats treated with thymalin corresponded with the time course in controls in contrast to thymectomized rats which did not receive the treatment. The results indicate that tuberculosis severity depends on the degree of immunodeficiency and that the functional properties of immunocompetent cells may be corrected with thymalin.

Topics: Adjuvants, Immunologic; Animals; Cell Migration Inhibition; Female; Immunologic Deficiency Syndromes; Leukocyte Count; Lymphocytes; Rats; Thymectomy; Thymus Hormones; Tuberculin; Tuberculin Test; Tuberculosis

The immune competence of the T lymphocyte system was studied in 28 noninstitutionalized subjects with Down's syndrome (DS) and were compared with sex- and age-matched healthy controls. The ability of enriched T lymphocytes to respond to 3 different T cell stimulants revealed a selective impairment of T lymphocyte subset(s). Subjects with DS showed normal responsiveness in allogeneic mixed lymphocyte reactions, but their response to phytohemagglutinin and in autologous mixed lymphocyte reactions was severely impaired. Non-T cells from DS subjects stimulated equally well both normal and DS allogeneic T lymphocytes. The blood concentration of serum thymic factor in the majority of DS subjects was much lower than that found in age-matched healthy controls. These data support the hypothesis that a deficiency of the T-dependent regulatory system is an intrinsic feature of DS and confirm the precocious aging of the immune system in these subjects.

Topics: Adolescent; Adult; Aging; Child; Down Syndrome; Female; Humans; Immunologic Deficiency Syndromes; Lymphocyte Culture Test, Mixed; Male; Phytohemagglutinins; T-Lymphocytes; Thymic Factor, Circulating; Thymidine; Thymus Hormones

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; DiGeorge Syndrome; Female; Humans; IgA Deficiency; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Rosette Formation; Thymic Factor, Circulating; Thymus Hormones

The activity of thymus-dependent serum factor SF was significantly lower in 18 children wit Down's syndrome (DS) than in 14 matched controls. The percentage of circulating T lymphocytes forming E-rosettes was also low in DS. Together with the previous finding of immature of T lymphocytes in peripheral blood, the present data suggest that the basic immune defect of DS is failure in differentiation of peripheral post-thymic precursors to fully immunocompetent T lymphocytes resulting from lack of thymic hormonal factors.

Topics: Child, Preschool; Down Syndrome; Humans; Immunologic Deficiency Syndromes; Infant; Rosette Formation; Thymic Factor, Circulating; Thymus Hormones; Trisomy

Arabian horses with severe combined immunodeficiency disease (SCID) were evaluated for thymic hormone activities using thymic extracts and sera. Extracts prepared from thymus of SCID horses were able to increase the number of spleen cells responding to sheep red blood cells in irradiated, bone marrow-reconstituted mice. In addition, ultrafiltrates prepared from sera of these immunodeficient horses, which contained material with molecular weight of less than 50,000 Daltons could (a) induce a population of human bone marrow precursor cells to differentiate into cells bearing SRBC receptors and form spontaneous E-rosettes, a characteristic of T lymphocytes, and (b) stimulate cyclic adenosine monophosphate (AMP) synthesis in mouse thymocytes. Based on in vivo and in vitro effects, it was concluded that the defect of these Arabian horses with severe combined immunodeficiency disease did not involve a complete thymic hormone inadequacy.

Topics: Aging; Animals; Binding Sites; Cattle; Cyclic AMP; Erythrocytes; Hemolytic Plaque Technique; Horses; Humans; Immunologic Deficiency Syndromes; Mice; Rosette Formation; Sheep; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland; Thymus Hormones

Topics: Humans; Immunologic Deficiency Syndromes; Rosette Formation; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones; Uremia

Topics: Animals; Candidiasis, Chronic Mucocutaneous; Cattle; Cell Differentiation; DiGeorge Syndrome; Epithelium; Humans; Immunologic Deficiency Syndromes; Mice; T-Lymphocytes; Thymic Factor, Circulating; Thymopoietins; Thymosin; Thymus Gland; Thymus Hormones; Wiskott-Aldrich Syndrome; Zinc

Topics: DiGeorge Syndrome; Fetus; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Infant; Lymphocyte Activation; Male; Rosette Formation; Thymic Factor, Circulating; Thymus Gland; Transplantation, Homologous