Thymosin Alpha-1 Introduction

Thymosin Alpha-1 is a biologically active peptide derived from prothymosin-alpha. Current hypotheses consider Thymosin Alpha-1 to be the main constituent of Thymosin Fraction-5, and as such, it is considered to be the active component that restores immune function in both athymic animals and animals with dysfunctional thymus glands. Thymosin Alpha-1 was among the first peptide isolates of Thymosin Fraction-5 to be sequenced and synthetically synthesized.

 

Thymosin Alpha-1 and Its Genetic Origins

In humans, the PTMA gene encodes prothymosin-alpha, a 113 amino-acid polypeptide. Thymosin Alpha-1 is a 28 amino-acid fragment of prothymosin-alpha, and research has shown that this fragment enhances the cell-mediated immune component of the human immune system. Its immune actions have enabled it to be used for treating viral infections such as Hepatitis B and Hepatitis C. It has also been incorporated into vaccines as an immune booster. Clinical studies have shown that Thymosin Alpha-1 can manage neoplasias by upregulating cytotoxic T-cells, which are involved in immune surveillance.

Thymosins: A Brief Overview

Thymosins are proteins with diverse biological actions found in numerous animal tissues. They were originally isolated from thymic tissues, hence their name. The main functions of thymosins are modulation and modification of biological responses. They stimulate leucopoiesis in the bone marrow, improving the immunocompetence status of an individual. Studies on isolated thymic extracts have shown that two types of thymosins, Thymosin Alpha-1 and Thymosin Beta-4, can be synthetically produced and used therapeutically for immunostimulation and immunomodulation.

Historical Discovery of Thymosins

Thymosins were discovered in the 1960s as researchers sought to identify, categorize, and study the biologically active humoral factors released by the thymus. These studies revealed that some isolates from the thymus gland restored immune functions, while others did not. These isolates were collectively termed Thymosin Fraction-5. Further analysis showed that Thymosin Fraction-5 comprised about 40 peptides, collectively termed thymosins. Electric field studies categorized these thymosins into alpha, beta, and gamma fractions. Molecular studies later revealed that these fractions are genetically and structurally unrelated.

Thymosin Alpha-1 in Immune Function

Recent studies on thymosins have shown that Thymosin Beta-1 is ubiquitin and that thymosins can be produced by cells outside the thymus. Research also showed that Thymosin Alpha-1 promotes the differentiation of T-cells in athymic mice and has immune-potentiating actions that interact with a dysfunctional thymus to normalize the immune status in children suffering from immunodeficiency.

Key Research Studies on Thymosin Alpha-1

Thymosin Alpha-1 and Cellular Immunity

In 1975, Goldstein et al. published a study titled “Thymosin Activity in Patients with Cellular Immunodeficiency” in The New England Journal of Medicine. The study aimed to investigate whether Thymosin Alpha-1 increases the number of T-cell rosettes. The subjects were two groups of patients: one with primary immunodeficiency and the other affected by a viral illness. Lymphocytes from these patients were incubated in-vitro with calf thymus extracts and sheep erythrocytes. The results showed an increase in T-cell populations until they reached normal levels.

A female patient with primary immunodeficiency secondary to thymic hypoplasia received Thymosin Alpha-1 in-vivo. Her T-cell rosettes increased by 33%, and she showed remarkable clinical improvement. However, she later developed delayed-type hypersensitivity reactions to Thymosin Alpha-1 extracted from calves. This study demonstrated that Thymosin Alpha-1 could partially reconstitute the cellular arm of the immune system in patients with thymic hypoplasia.

Thymosin Alpha-1 and Expression of Lymphocytic Interleukin-2 Receptors

In 1990, Kimberly D. Leichtling, Marcelo B. Sztein, and Susana A. Serrate published a study titled “Thymosin Alpha-1 Modulates the Expression of High Affinity Interleukin-2 Receptors on Normal Human Lymphocytes” in the International Journal of Immunopharmacology. This study aimed to investigate the effects of Thymosin Alpha-1 (abbreviated as Tα1) on high-affinity IL-2R (interleukin-2 receptors). Peripheral lymphocytes from healthy individuals were used. The results showed that Tα1 increased the population of high-affinity IL-2R expressed by the lymphocytes and increased interleukin-2 production. Peak responses to Tα1 occurred at concentrations of 10−12M and 10−8M. Flow cytometry studies showed that Tα1 upregulated Tac antigen expression but had no effect on the affinity of IL-2R for its ligands. Tα1 demonstrated no effect in lymphocytes not subjected to mitogenic stimulation.

This study concluded that Thymosin Alpha-1 modulates the immune function by increasing the expression of interleukin-2 and its corresponding receptors (IL-2R). Interleukin-2 promotes lymphopoiesis, suggesting that the upregulation of both IL-2 and IL-2R expression increases the T-cell population.

Thymosin Alpha-1 and Chronic Hepatitis C

In 1995, Rasi et al. published their study titled “Combination Thymosin Alpha-1 and Lymphoblastoid Interferon Treatment in Chronic Hepatitis C” in the British Medical Journal. The study assessed the effect of combination therapy on chronic hepatitis C. Fifteen chronic hepatitis C patients, positive for Hepatitis C Virus RNA (HCV RNA), participated. Four patients had failed standard interferon monotherapy, and the rest were treatment-naïve. All patients received the combination therapy for 12 months and were followed up for the next six months.

The results showed that seven patients were HCV RNA negative after six months of combination therapy. By the end of the treatment, this number increased to eleven, including two who had failed standard interferon monotherapy. During the follow-up period, six of the eleven patients showed a sustained HCV RNA negative status. This study concluded that the combination therapy of Thymosin Alpha-1 and interferon provides potential benefits in managing chronic hepatitis C disease.

 

Conclusion

The studies reviewed above demonstrate that Thymosin Alpha-1 can clinically improve immune status. Thymosin Alpha-1 partially reconstitutes the cellular arm of the immune system by increasing the number of T-cell rosettes in patients with thymic hypoplasia. It modulates immune function by upregulating the expression of IL-2 and IL-2R and has shown great promise in managing chronic hepatitis C.

Thymosin Alpha-1 represents a significant advancement in peptide research, offering insights and potential treatments for various immune-related conditions. As researchers continue to explore its applications, Thymosin Alpha-1 may provide further therapeutic benefits, enhancing our understanding and capability to manipulate the immune system for better health outcomes.