thymic-factor--circulating and Lupus-Erythematosus--Systemic

Topics: Antilymphocyte Serum; Autoantibodies; B-Lymphocytes; Cell Nucleus; Female; Humans; Immunity, Cellular; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Mitogens; Receptors, Fc; Ribonucleoproteins; Rosette Formation; T-Lymphocytes; T-Lymphocytes, Regulatory; Thymic Factor, Circulating

Topics: Animals; Antibody-Dependent Cell Cytotoxicity; Antilymphocyte Serum; Autoantibodies; B-Lymphocytes; Blood Cell Count; Dogs; Female; Humans; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Mice; Skin Tests; T-Lymphocytes; Thymic Factor, Circulating

Thymic serum activity (TSA) has been studied in 52 healthy subjects, 48 rheumatoid arthritis patients and 17 sufferers with systemic lupus erythematosus aged from 18 to 70. TSA was compared in patients under and over 40 years. In those under 40 TSA appeared significantly inhibited, while in older subjects it did not differ from age-matched control. No correlations were reported between TSA levels and clinical characteristics. Changes in TSA levels may be related both to low content of thymic hormones and formation of inactive complexes from thymic mediators with inhibitors.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Chronic Disease; Humans; Lupus Erythematosus, Systemic; Middle Aged; Thymic Factor, Circulating

Thymulin is a nonapeptide hormone isolated from the thymus gland. It has immunomodulatory effects which have not yet been well defined. Its major actions have been shown to be on T-cells and their immature precursors. In this study, thymulin was tested in vitro for its effect on the release of IL-1 alpha, IL-2, IL-6 and TNF alpha from peripheral blood mononuclear cells (PBMC) obtained from normal volunteers and patients with active systemic lupus erythematosus (SLE). In our experiments, PBMC (stimulated with LPS or PHA) were cultured for 24 h in the presence of 1,100 or 1,000 ng/ml of thymulin. Supernatants were subsequently assayed for cytokine activities using commercially available ELISA (IL-2, IL-6 and TNF alpha) and RIA (IL-1 alpha) kits. Thymulin (1 ng/ml) resulted in a significant (p < 0.01) increase in IL-1 alpha in the volunteers and a significant (p < 0.05) inhibition of this cytokine at all dose levels tested in SLE patients, whose basal levels of IL-1 alpha were significantly (p < 0.05) higher. Thymulin significantly (p < 0.05) inhibited IL-2 only in SLE patients at 1,000 ng/ml. At all dose levels tested, thymulin significantly (p < 0.01) inhibited IL-6 in volunteers, and, only at 1,000 ng/ml, it significantly (p < 0.05) inhibited it in patients with SLE. At the 1,000 ng/ml dose level, TNF alpha was significantly (p < 0.05) inhibited in both volunteers and SLE patients, whose basal levels of this cytokine were significantly (p < 0.05) higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukins; Leukocytes, Mononuclear; Lipopolysaccharides; Lupus Erythematosus, Systemic; Middle Aged; Phytohemagglutinins; Radioimmunoassay; Thymic Factor, Circulating; Tumor Necrosis Factor-alpha

Topics: Adolescent; Adult; Animals; Arthritis, Rheumatoid; Female; Humans; Lupus Erythematosus, Systemic; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Thymectomy; Thymic Factor, Circulating; Zinc

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.

Topics: Animals; Antibodies, Antinuclear; Breeding; Dogs; Joints; Kidney; Lupus Erythematosus, Systemic; Lymphopenia; Skin; T-Lymphocytes; Thrombocytopenia; Thymic Factor, Circulating

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.

Topics: Animals; Antibodies, Antinuclear; Autoimmune Diseases; Disease Models, Animal; Dog Diseases; Dogs; Female; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Pedigree; T-Lymphocytes; Thymic Factor, Circulating

The influence of thymic humoral factor, THF, on systemic lupus erythematosus, SLE, lymphocyte function was investigated. Increasing numbers of SLE T-cells, rosetted at 4 degrees C or 37 degrees C, were cultured with allogeneic normal B-cells and the change in IgM synthesis was assessed. Lymphocytes of some SLE patients showed improved suppression with THF when rosetted at 37 degrees C. Normal control lymphocytes did not show a net change in suppression with THF. The subgroup of SLE patients that showed improved suppression with THF in vitro might be a more appropriate group for in vivo therapeutic trials with thymic hormone, TH, than SLE patients in general.

Topics: B-Lymphocytes; Cell Separation; Female; Humans; Immunoglobulin M; Lupus Erythematosus, Systemic; Lymphocytes; Male; Rosette Formation; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones

Perturbations in T cells and T cell subsets of peripheral blood lymphocytes were looked for, using monoclonal antibodies, in nine patients with rheumatoid arthritis (RA) and four patients with systemic lupus erythematosus (SLE). All SLE patients were in an acute phase of their disease, but had not yet received steroids. Seven of the nine RA patients presented an active illness, recently diagnosed in five cases, and received no steroids nor D-penicillamin. T cell subsets alterations responsible for abnormal values of the OKT4 +/OKT8 + immunoregulatory ratio, were improved by in vitro incubation of the lymphocytes with synthetic thymulin in eight out of nine RA patients. No significant modification occured for SLE patients' lymphocytes. These results support the possible beneficial role of thymulin in the treatment of rheumatoid arthritis.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Surface; Arthritis, Rheumatoid; Female; Humans; In Vitro Techniques; Leukocyte Count; Lupus Erythematosus, Systemic; Male; Middle Aged; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones

Topics: Adult; Cells, Cultured; Female; Humans; Lupus Erythematosus, Systemic; Lymphocyte Culture Test, Mixed; Mixed Connective Tissue Disease; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones

Topics: Adolescent; Aging; Female; History, 16th Century; Humans; Lupus Erythematosus, Systemic; Male; T-Lymphocytes; Thymic Factor, Circulating; Thymopoietins; Thymus Gland; Thymus Hormones

We have recently described that human autologous rosette-forming (Tar) cells have the characteristics of postthymic precursor cells. Herein we report that we found circulating Tar cells significantly diminished in 32 patients with untreated systemic lupus erythematosus (SLE) as compared to 32 age/sex matched controls. Pretreatment of peripheral blood mononuclear cells (MNC) from SLE patients with serum from young normal adults or wtih serum thymic factors (FTS) increased their percentages of Tar cells significantly but reached near normal values in only 3 patients with inactive disease. Patients and normal subjects had similar percentages of Tar cells binding peanut-agglutinin. Characteristic functions of postthymic precursor cells are feedback inhibition and generation of suppressor cells which we studied in systems where we depleted or added Tar cells to Tmu and B cells, or MNC, respectively, using as indicators the production of immunoglobulins measured in culture supernatants or 3H-thymidine incorporation. We found both functions diminished in SLE patients despite using the presence of a qualitative as well as quantitative defect. In two SLE patients studied both of these functions corrected partially when their Tar cells were pretreated with FTS. In 20 SLE patients we studied Tgamma and Tmu cells as well as Concanavalin-A-induced, spontaneously-expanded suppression and found Concanavalin-A-induced, spontaneously-expanded suppressor function and Tgamma cells diminished. However only the reduction of Tgamma and of spontaneously-expanded suppressor function were found to relate to disease activity. On the other hand, Tmu cells were found to be similar in numbers in SLE patients and normal controls.

Topics: Adult; Concanavalin A; Feedback; Female; Humans; Lupus Erythematosus, Systemic; Male; Receptors, Fc; Rosette Formation; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones

Determination of the specificities of antinuclear antibodies in the sera of 20 dogs presenting with symptoms of a lupus-like syndrome permitted their separation into 2 groups. The first group of 14 dogs all had antibody activity to DNA-histone antigen(s), and 4 of them also had antibodies to native DNA (nDNA). The Farr test with standard buffer was found to be unsatisfactory for the measurement of anti-nDNA antibodies in dog sera due to a high incidence of false positive reactions; these could be eliminated by the inclusion of sodium dodecyl sulfate in the buffer system. The second group of 6 dogs was characterized by the presence of antibodies to extractable nuclear antigen. In every serum tested diseased dogs had a diminished level of circulating thymic factor as compared to controls of the same age, suggesting that a diminution of suppressor T cells may be an etiologic factor.

Topics: Animals; Antibodies, Antinuclear; Antibody Specificity; Autoantibodies; DNA; Dog Diseases; Dogs; False Positive Reactions; Female; Lupus Erythematosus, Systemic; Male; Thymic Factor, Circulating