The thymosins are a family of hormonal-like peptides which in combination with cytokines, T-cells, B cells, dendritic cells, and macrophages, help to provide an immune umbrella for combating pathogenes, destroying malignant cells and regulating wound healing and angiogenesis. Thymic derived peptides isolated from thymosin fraction 5 also play a more general physiological role and have been found to influence a number of endocrine and neuroendocrine pathways. Biological response modifiers such as thymosin-α1 (Tα1), are produced in significant quantities within the thymus whereas other for example, thymosin-β4 (Tβ4), the major actin sequestering peptide in cells are more ubiquitous in nature and are found in highest concentrations in blood platelets, neutrophils, macrophages and a wide variety of other cell types.
Recent studies have established that Toil can block in a time and dose dependent fashion glucocorticoid (GC) induced apoptosis of immature thymocytes. Apoptosis of developing thymocytes is a crucial process in the development of T-cell immunity. The life and death of thymocytes (as well as other cells), is a crucial balance of microenvironmental and intracellular signaling. Apoptosis of thymocytes is influenced by interaction between developing thymocytes and the microenvironment of the thymus. This finding may further help to characterize other potential therapeutic applications for Tα1. Current studies demonstrate the potential for Tα1 in modulating the effects of GC induced immunosuppression and suppression of thymic function. Results from this study and previous studies suggest that Tα1 can potentially protect non-selected thymocytes from GC induced depletion within the thymus thus allowing for increased time for selection and production of new thymocytes.
Clinically, Tα1, is now approved in 21 countries and has been utilized for the treatment of patients with cancer and immune deficiency disorders including AIDS, chronic hepatitis B (HepB), and hepatitis C (HepC) and as an adjuvant to enhance the efficacy of vaccines in the elderly and in immunocompromised patients. Tα1 is active as a monotherapy for HepB and in combination with interferon, in HepC. It has a very good safety profile. Tβ4 was first characterized by its ability to stimulate the expression of terminal deoxynucleotidyl transferase, a non-template directed DNA polymerase in bone marrow stem cells and to inhibit macrophage migration. Known, that it is the major actin sequestering peptide in normal mammalian cells and plays an important role in the remodeling and healing of tissues. Tβ4 has been found to accelerate wound healing and angiogenesis in a variety of in vitro and in vivo models. Tβ4 represents a new class of wound healing compound. It is not a growth factor or cytokine but rather exhibits a number of physiological properties which include its ability to sequester and regulate actin, its potent chemotactic properties (specifically for endothelial cells), and its capability to down regulate a number of inflammatory cytokines that are present in chronic wounds.
Over the past few years, remarkable progress has been made in the biochemical and clinical characterization of many of the major isoforms of Tβ4 in both normal and abnormal cells. To date, about 20 isoforms of Tβ4 have been identified. Using microarray analysis, it has now been established that a number of β thymosins are regulated in a variety of disease states including cancer. Studies are currently underway to determine whether characterization of specific β-thymosins including an isoform of Tβ4 not found in normal tissue will be useful in helping to diagnose specific disease entities and to develop new therapeutics for treatment.
The work was submitted to international scientific conference «Basic and applied research in medicine» , Nov. 26 - Dec. 4, 2008 China (Beijing), came to the editorial office 08.08.2008.