Disease relevance of THYMOPENTIN

• Thymopentin in Sézary syndrome [1].
• Thymopentin as adjuvant in non-responders or hyporesponders to hepatitis B vaccination [2].
• Response to thymopoietin pentapeptide in patient with DiGeorge syndrome [3].
• 4 weeks after the end of the TP-5 therapy, the improvement was still present although there was a trend towards relapses [4].
• Abnormality of T cells in cases of hyper-IgE syndrome was not corrected by TP-5 treatment [5].

Psychiatry related information on THYMOPENTIN

• Administration of thymopentin to patients with phobic disorders improves depressed phagocytic functions [6].

High impact information on THYMOPENTIN

• T cell development in normal and thymopentin-treated nude mice [7].
• Treatment of active rheumatoid arthritis with slow intravenous injections of thymopentin. A double-blind placebo-controlled randomised study [4].
• In 5 patients with ataxia-telangiectasia clinical manifestations and immunological tests were unchanged by TP-5 [5].
• However, two thymomimetic drugs, isoprinosine and diethyldithiocarbamate, inhibit the development of infections in patients with pre-AIDS in large multicenter trials, and preliminary data from trials with two thymomimetic peptides, thymopentin and ImReg-1, in pre-AIDS patients are encouraging [8].
• Synthetic pentapeptides corresponding to residues 32-36, called thymopentin and splenopentin, reproduce biological activities of thymopoietin and splenin, respectively [9].

Chemical compound and disease context of THYMOPENTIN

• Furthermore, thymopentin delays HIV disease progression in the presence of a key ZDV resistance mutation as well as high viral load and low CD4+ T-cell counts [10].
• CONCLUSION: The combination of 5-FU + FA and TP-5 + IL-2 is effective in advanced colorectal cancer with acceptable toxicity [11].
• Sequential biochemotherapy for metastatic colorectal cancer using fluorouracil, folinic acid, thymopentin and interleukin-2: clinical and immunological effects [11].
• Use of subcutaneous thymopentin in the treatment of steroid-dependent relapsing minimal-change nephrotic syndrome [12].
• OBJECTIVE: Immunomodulatory therapies in cutaneous lymphoma are reviewed, including interferons, interleukin-2, cyclosporin A, monoclonal antibodies, autologous bone marrow transplantation, fusion toxins, thymopentin and extracorporeal photopheresis as well as recently reported methods such as vaccination therapy, mycophenolate, and new retinoids [13].

Biological context of THYMOPENTIN

• CD10 is expressed on human thymic epithelial cell lines and modulates thymopentin-induced cell proliferation [14].
• Effect of thymopoietin pentapeptide (TP5) on autoimmunity. I. TP5 suppression of induced erythrocyte autoantibodies in C3H mice [15].
• In a prospective randomized trial, the immunorestorative potential of a combined therapy with the thymomimetic substance Thymopentin (TP-5; Timunox, Cilag GMBH, Sulzbach, FRG) and the cyclooxygenase inhibitor indomethacin (Indo) in 60 patients (mean age, 63 +/- 2 years) undergoing open heart surgery was studied [16].
• The LGL generated following TP-5 injection had a T3+Leu11- surface phenotype and low NK activity [17].
• Cooperativity of thymopoietin 32-36 (the active site) and thymopoietin 38-45 in receptor binding [18].

Anatomical context of THYMOPENTIN

• Thus thymopoietin and thymopentin affect neuromuscular transmission and induce the phenotypic differentiation of T precursor cells in vitro while inhibiting phenotypic differentiation of B cells [9].
• Therapy with biologic response modifiers, such as interferon gamma or thymopentin, is oriented toward normalization of imbalanced immune responsiveness, rather than direct suppression of the immune system [19].
• He showed a marked increase in large granular lymphocytes (LGL) both during the treatment with TP-5 and after BMT [17].
• A boy with combined immunodeficiency having low natural killer (NK)-cell activity received thymopoietin pentapeptide (TP-5) treatment, transplanted with T cell-depleted HLA-haploidentical bone marrow (BMT) cells from his father and with thymus tissue from an infant at different times during the first year of life [17].
• We identified monocytes and neutrophils as TP5-binding cells by displacing fluorescein-labelled TP5 with an excess of unlabelled TP5 in competition assays [20].

Associations of THYMOPENTIN with other chemical compounds

• Immunomodulatory therapy with thymopentin and indomethacin. Successful restoration of interleukin-2 synthesis in patients undergoing major surgery [16].
• The TP-5 pentapeptide analog of thymopoietin and the SP-5 pentapeptide analog of splenin, which differ only in substitution of Glu for Asp and represent positions 32-36 of the parent molecules, were compared for effects on the capacity of C3H/HeJ female mice to reject C3H/HeJ male skin (the H-Y rejection response) [21].
• The spontaneously metastatic murine pancreatic tumor, PAN 2, was used to evaluate established regimens of combined chemoimmunotherapy with 5-fluorouracil (5-FU) and levamisole and new protocols based on the immunomodulator, thymopoietin pentapeptide (TP-5) [22].
• Immunomodulatory therapy consisted of the cyclooxygenase inhibitor indomethacin, which blocks the downregulating agent prostaglandin E2, and thymopentin, which enhances T-lymphocytic activity [23].
• Thymopoietin 28-39 corresponds to an antigenic hydrophilic region of thymopoietin that contains the pentapeptide active site (thymopoietin 32-36, Arg-Lys-Asp-Val-Tyr) [24].

Gene context of THYMOPENTIN

• The thymopentin-treated mice produce enhanced levels of IL-2 and IFN-gamma, but significantly reduced amounts of IL-4 [25].
• The effects of thymopentin on the development of SLE-like syndrome in the MRL/lpr-lpr mouse [26].
• Immune imbalance in the synovial fluid of rheumatoid arthritis patients: effects of intra-articular injection of thymopentin [27].
• On the basis of these results, an intra-articular immunomodulating treatment with thymopentin has been performed: its effects were characterized by an increase of CD8+CD11b+ T cells in the CD8 subset parallel to the enhancement of the suppressor-inducer/naive T cells in the CD4 subset with a statistically significant correlation [27].
• The examination of immunomodulatory properties of oligopeptides derived from two exposed loops (containing thymopentin-like and tuftsin-like sequences, respectively) of the proteins belonging to TGF beta family suggests that the particular species of the TGF beta family should differ distinctly in their influence on the immune response [28].

Analytical, diagnostic and therapeutic context of THYMOPENTIN

• Western immunoblotting assays showed that the BLT-1-reactive membrane antigen is a 22,000 m.w. protein which was inducible in bovine thymocytes with bovine thymic hormones, thymosin fraction 5, thymosin alpha 1, and thymopentin ORF-18150, indicating that it is a mature T lymphocyte differentiation antigen [29].
• The prognostic significance of serum viral load, codon 215 reverse transcriptase mutation and CD4+ T cells on progression of HIV disease in a double-blind study of thymopentin [10].
• Patients were randomized to receive either thymopentin (Timunox, n = 48) or placebo (n = 52), administered as daily subcutaneous injections for 6 weeks [30].
• As reported previously, the capacity of C3H/HeJ female mice to reject C3H/HeJ male skin was raised by thymectomy, or with age, and treatment with TP-5 substantially normalized the rejection response [31].
• Patients were then randomly assigned to a control group or to a group receiving thymopentin [32].

References