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Thymosin Alpha

Thymosin Alpha 1

Thymosin alpha 1 (T α 1) is a peptide (consists of two or more amino acids linked in a chain) that is naturally produced by the thymus gland. It plays an integral role in the maturation of immune system cells known as T-cells, which are vital in fighting harmful bacteria, fungi, or viruses. Thymosin alpha 1 also has anti-inflammatory and anti-fatigue properties and is given in patients with hepatitis B and C, malignant melanoma, liver cancer, drug-resistant tuberculosis, Lyme disease and Di George’s syndrome (immunodeficiency disease).

Overall Health Benefits of Thymosin Alpha 1

  • Eradicates bacteria, virus, and fungi [1-7]
  • Boosts the function of certain immune cells [8-18]
  • Suppresses cancer and tumor growth [19-35]
  • Accelerates the wound healing process [36-38]
  • Fights inflammation [39-48]
  • Increases vaccine effectiveness [49-53]
  • Improves cognitive function [54]

Proven Health Benefits of Thymosin Alpha 1

Eradicates Bacteria, Virus, and Fungi

Thymosin alpha 1 possesses strong antimicrobial properties that can help ward off infection:

  1. In patients with severe sepsis (presence of harmful microorganisms in the blood), thymosin alpha 1 administration improved clinical outcome without any adverse effect. [1]
  2. In patients with chronic hepatitis B and C, thymosin alpha 1 administration for 6 months normalized liver enzyme levels, which is suggestive of improved liver function. [2-4]
  3. In mice with fungal infection, thymosin alpha 1 increased the production of phagocytes, which are cells capable of engulfing and absorbing bacteria. [5]
  4. Thymosin alpha 1-based immunomodulatory therapy was associated with a significant reduction in mortality in septic patients. [6]
  5. Thymosin alpha 1 administration in septic patients was also associated with increased survival rate, alleviation of illness, and short ICU stay and mechanical ventilation time. [7]

Boosts the Function of Certain Immune Cells

By affecting the production of certain immune cells, thymosin alpha 1 exerts its immune-boosting properties:

  1. Thymosin alpha 1 is known to augment T-cell function. [8-9]
  2. Thymosin alpha 1 also helps regulate both the innate and adaptive immune systems. [10-11]
  3. Thymosin alpha 1 has the ability to increase CD4+/CD8+ ratio. [12-13]
  4. By activating and stimulating certain signaling pathways, thymosin alpha 1 boosts the production of immune-related cytokines. [14]
  5. By selectively stimulating the release of luteinizing hormone (LH), thymosin alpha 1 indirectly strengthens the immune function. [15]
  6. In patients with sepsis, thymosin alpha 1 restored the dysregulated immune response. [16-17]
  7. A cell study found that thymosin alpha 1 inhibited HIV-1 and human T lymphotropic virus 1 infection by stimulating the release of CD8(+) cells. [18]

Suppresses Cancer and Tumor Growth

There’s also increasing evidence supporting the anti-cancer and antitumor properties of thymosin alpha 1:

  1. By regulating cytokine secretion and repairing damaged immune system, thymosin alpha 1 may help reduce cancer incidence. [19]
  2. In stage IV human breast cancer model, thymosin alpha 1 treatment was associated with significantly slow tumor growth. [20]
  3. In patients with metastatic melanoma and advanced non-small cell lung cancer, thymosin alpha 1 treatment prolonged survival. [21]
  4. In patients with hepatitis B virus-associated liver cancer, thymosin alpha 1 therapy improved liver function and significantly prolonged recurrence‑free and overall survival. [22]
  5. Thymosin alpha 1 exerts its anti-tumor effects mainly by increasing the secretion of various T cell lymphokines, activating T4 helper cells to promote lymphocyte activity, and increasing the cytotoxicity of natural killer cells. [23-25]
  6. Administration of thymosin alpha 1 in cancer patients was associated with reduced risk of dying and improved disease‐/progression‐free survival. [26]
  7. In patients with metastatic lung cancer, thymosin alpha 1 treatment was associated with complete disappearance of lesions. [27]
  8. A cell study found that exposure of human breast cancer cells to thymosin alpha 1 induced apoptosis (programmed cell death). [28]
  9. Administration of thymosin alpha 1 in cancer patients increased the anti-tumor effect of chemotherapy while markedly reducing side effects of the treatment. [29]
  10. In tumor-bearing mice, thymosin alpha 1 significantly delayed tumor growth and prolonged survival time. [30]
  11. When combined with human immunoglobulin, thymosin alpha 1 can produce stronger chemotherapeutic effect against breast cancer cells in mice. [31]
  12. When combined with the chemotherapeutic drug dacarbazine, thymosin alpha 1 can improve overall survival of patients with metastatic melanoma (cancer that spreads to other sites). [32-33]
  13. In human lung cancer cell lines, thymosin alpha 1 administration inhibited cellular proliferation and cell migration through its antioxidant properties. [34-35]

Accelerates the Wound Healing Process

Studies also show that thymosin alpha 1 can accelerate tissue recovery:

  1. When given either topically or in the form of injections, thymosin alpha 1 accelerated wound healing in mice. [36]
  2. A cell-based study found that thymosin alpha 1 accelerates wound healing by promoting formation of new blood vessels and cell migration at the site of injury. [37]
  3. In rat kidney cells, thymosin alpha 1 prevented programmed cell death and renal scarring. [38]

Fights Inflammation

There’s also a good deal of evidence suggesting that thymosin alpha 1 has potent anti-inflammatory properties:

  1. In rats with acute liver failure, thymosin alpha 1 reduced liver inflammation. [39]
  2. Thymosin alpha 1 may help prevent tissue injury by reducing the release of inflammatory factors and cytokines, and the levels of IL-10 to control inflammation. [40-41]
  3. Thymosin alpha 1 also reduces inflammation by suppressing pro-inflammatory TNF-α. [42-45]
  4. A cell-based study also found that thymosin alpha 1 protects against inflammatory allergy. [46]
  5. A 2019 study published in the Neuroscience Bulletin found that thymosin alpha 1 inhibited pro-inflammatory cytokines in the spinal cord. [47]
  6. In a mouse model of cystic fibrosis, a condition characterized by abnormal production of thick mucus, thymosin alpha 1 administration reduced inflammation. [48]

Increases Vaccine Effectiveness

Thymosin alpha 1 is the ultimate immune system booster. Studies show that this peptide can naturally enhance the effectiveness of certain vaccines:

  1. In patients who are susceptible to infection, thymosin alpha 1 administration enhanced the immunogenicity (ability to provoke an immune response) of the pandemic influenza vaccine. [49]
  2. In elderly patients, administration of thymosin alpha 1 together with influenza vaccine enhanced vaccine responses. [50-51]
  3. In animal models, thymosin alpha 1 enhanced the efficacy of the classical swine fever vaccine. [52]
  4. A study found that thymosin alpha 1 can increase vaccine effectiveness by restoring immune system homeostasis. [53]

Improves Cognitive Function

A 2017 study published in the Neuroscience bulletin found that administration of thymosin alpha 1 in neonatal mice improved cognitive function. Compared with the control group, thymosin alpha 1-treated mice had better cognitive abilities in early life, increased levels of growth factors, and decreased levels of inflammatory substances. [54]

References:

  1. Wu J, Zhou L, Liu J, et al. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care. 2013;17(1):R8. Published 2013 Jan 17. doi:10.1186/cc11932.
  2. Ancell CD, Phipps J, Young L. Thymosin alpha-1. Am J Health Syst Pharm. 2001;58(10):879-85.
  3. You J, Zhuang L, Cheng HY, Yan SM, Yu L, Huang JH, Tang BZ, Huang ML, Ma YL, Chongsuvivatwong V, et al. World J Gastroenterol. Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: 2006 Nov 7; 12(41): 6715-21.
  4. Sherman KE, Sjogren M, Creager RL, Damiano MA, Freeman S, Lewey S, Davis D, Root S, Weber FL, Ishak KG, et al. Hepatology. Combination therapy with thymosin alpha1 and interferon for the treatment of chronic hepatitis C infection: a randomized, placebo-controlled double-blind trial. 1998 Apr; 27(4):1128-35.
  5. Romani L, Bistoni F, Gaziano R, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103(11):4232-9.
  6. Li C, Bo L, Liu Q, Jin F. Thymosin alpha1 based immunomodulatory therapy for sepsis: a systematic review and meta-analysis. Int J Infect Dis. 2015;33:90-6.
  7. Feng Yun Wang, Bin Fang, Xin Hua Qiang, et al., “The Efficacy and Immunomodulatory Effects of Ulinastatin and Thymosin α1 for Sepsis: A Systematic Review and Meta-Analysis,” BioMed Research International, vol. 2016, Article ID 9508493, 8 pages, 2016. https://doi.org/10.1155/2016/9508493.
  8. Serrate SA, Schulof RS, Leondaridis L, Goldstein AL, Sztein MB. Modulation of human natural killer cell cytotoxic activity, lymphokine production, and interleukin 2 receptor expression by thymic hormones. J Immunol. 1987;17:2338–2343.
  9. Sztein MB, Serrate SA. Characterization of the immunoregulatory properties of thymosin alpha 1 on interleukin-2 production and interleukin-2 receptor expression in normal human lymphocytes. Int J Immunopharmacol. 1989;17:789–800. doi: 10.1016/0192-0561(89)90133-1.
  10. Romani L, Bistoni F, Montagnoli C, Gaziano R, Bozza S, Bonifazi P, Zelante T, Moretti S, Rasi G, Garaci E, Puccetti P. Thymosin alpha1: an endogenous regulator of inflammation, immunity, and tolerance. Ann N Y Acad Sci. 2007;17:326–338. doi: 10.1196/annals.1415.002.
  11. Pierluigi B, D’Angelo C, Fallarino F, Moretti S, Zelante T, Bozza S, De Luca A, Bistoni F, Garaci E, Romani L. Thymosin alpha1: the regulator of regulators? Ann N Y Acad Sci. 2010;17:1–5. doi: 10.1111/j.1749-6632.2010.05465.x.
  12. Zhang Y, Chen H, Li YM, Zheng SS, Chen YG, Li LJ, Zhou L, Xie HY, Praseedom RK. Thymosin alpha1- and ulinastatin-based immunomodulatory strategy for sepsis arising from intra-abdominal infection due to carbapenem-resistant bacteria. J Infect Dis. 2008;17:723–730. doi: 10.1086/590500.
  13. Wang X, Li W, Niu C, Pan L, Li N, Li J. Thymosin alpha 1 is associated with improved cellular immunity and reduced infection rate in severe acute pancreatitis patients in a double-blind randomized control study. Inflammation. 2011;17:198–202. doi: 10.1007/s10753-010-9224-1.
  14. King R, Tuthill C. Immune Modulation with Thymosin Alpha 1 Treatment. Vitam Horm. 2016;102:151-78.
  15. Milenkovic L, Mccann SM. Effects of thymosin alpha-1 on pituitary hormone release. Neuroendocrinology. 1992;55(1):14-9.
  16. Pei F, Guan X, Wu J. Thymosin alpha 1 treatment for patients with sepsis. Expert Opin Biol Ther. 2018;18(sup1):71-76.
  17. Goldstein AL, Goldstein AL. From lab to bedside: emerging clinical applications of thymosin alpha 1. Expert Opin Biol Ther. 2009;9(5):593-608.
  18. Matteucci C, Minutolo A, Pollicita M, et al. Thymosin α 1 potentiates the release by CD8(+) cells of soluble factors able to inhibit HIV-1 and human T lymphotropic virus 1 infection in vitro. Expert Opin Biol Ther. 2015;15 Suppl 1:S83-100.
  19. Wang F, Yu T, Zheng H, Lao X. Thymosin Alpha1-Fc Modulates the Immune System and Down-regulates the Progression of Melanoma and Breast Cancer with a Prolonged Half-life. Sci Rep. 2018;8(1):12351. Published 2018 Aug 17. doi:10.1038/s41598-018-30956-y.
  20. Shrivastava P, Singh SM, Singh N. Activation of tumor-associated macrophages by thymosin alpha 1. Int J Immunopathol Pharmacol. 2004;17(1):39-47.
  21. Garaci E, Pica F, Serafino A, et al. Thymosin α1 and cancer: action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012;1269:26-33.
  22. Liang YR, Guo Z, Jiang JH, Xiang BD, Li LQ. Thymosin α1 therapy subsequent to radical hepatectomy in patients with hepatitis B virus-associated hepatocellular carcinoma: A retrospective controlled study. Oncol Lett. 2016;12(5):3513–3518. doi:10.3892/ol.2016.5121.
  23. Garaci E, Pica F, Serafino A, Balestrieri E, Matteucci C, Moroni G, Sorrentino R, Zonfrillo M, Pierimarchi P, Sinibaldi-Vallebona P. Thymosin α1 and cancer: Action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012;1269:26–33. doi: 10.1111/j.1749-6632.2012.06697.x.
  24. Cheng SQ, Wu MC, Chen H, Shen F, Yang JH, Zhao YX, Mo ZW. Influence of thymosin α1 on postoperative recurrence of primary liver cancer. Chin J Hepatobil Surg. 2004;10:592–593.
  25. Palmieri G, Biondi E, Morabito A, Rea A, Bianco A. Could thymostimulin prevent hepatocellular carcinoma occurrence in patients with liver cirrhosis? Oncol Rep. 1996;3:655–656.
  26. Wolf E, Milazzo S, Boehm K, Zwahlen M, Horneber M. Thymic peptides for treatment of cancer patients. Cochrane Database Syst Rev. 2011;(2):CD003993.
  27. Lee D, Kim SS, Seong S, Cho W, Yu H. Stage IV Wilms Tumor Treated by Korean Medicine, Hyperthermia and Thymosin-α1: A Case Report. Case Rep Oncol. 2016;9(1):119-25.
  28. Guo Y, Chang H, Li J, et al. Thymosin alpha 1 suppresses proliferation and induces apoptosis in breast cancer cells through PTEN-mediated inhibition of PI3K/Akt/mTOR signaling pathway. Apoptosis. 2015;20(8):1109-21.
  29. Garaci E, Pica F, Rasi G, Favalli C. Thymosin alpha 1 in the treatment of cancer: from basic research to clinical application. Int J Immunopharmacol. 2000;22(12):1067-76.
  30. Shrivastava P, Singh SM, Singh N. Effect of thymosin alpha 1 on the antitumor activity of tumor-associated macrophage-derived dendritic cells. J Biomed Sci. 2004;11(5):623-30.
  31. Shen X, Li Q, Wang F, et al. Generation of a novel long-acting thymosin alpha1-Fc fusion protein and its efficacy for the inhibition of breast cancer in vivo. Biomed Pharmacother. 2018;108:610-617.
  32. Maio M, Mackiewicz A, Testori A, et al. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. J Clin Oncol. 2010;28(10):1780-7.
  33. Danielli R, Fonsatti E, Calabrò L, Di giacomo AM, Maio M. Thymosin α1 in melanoma: from the clinical trial setting to the daily practice and beyond. Ann N Y Acad Sci. 2012;1270:8-12.
  34. Kharazmi-khorassani J, Asoodeh A. Thymosin alpha-1; a natural peptide inhibits cellular proliferation, cell migration, the level of reactive oxygen species and promotes the activity of antioxidant enzymes in human lung epithelial adenocarcinoma cell line (A549). Environ Toxicol. 2019;34(8):941-949.
  35. Kharazmi-khorassani J, Asoodeh A, Tanzadehpanah H. Antioxidant and angiotensin-converting enzyme (ACE) inhibitory activity of thymosin alpha-1 (Thα1) peptide. Bioorg Chem. 2019;87:743-752.
  36. Malinda KM, Sidhu GS, Banaudha KK, et al. Thymosin alpha 1 stimulates endothelial cell migration, angiogenesis, and wound healing. J Immunol. 1998;160(2):1001-6.
  37. Available from https://www.federallabs.org/technology/thymosin-alpha-1-promotes-tissue-repair-angiogenesis-and-cell-migration.
  38. Yang X, Chen Y, Zhang J, et al. Thymosin α1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure. Exp Ther Med. 2018;15(4):3231–3238. doi:10.3892/etm.2018.5843.
  39. Romani L, Bistoni F, Gaziano R, Bozza S, Montagnoli C, Perruccio K, Pitzurra L, Bellocchio S, Velardi A, Rasi G, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103:4232–4239. doi: 10.1182/blood-2003-11-4036.
  40. Bozza S, Gaziano R, Bonifazi P, Zelante T, Pitzurra L, Montagnoli C, Moretti S, Castronari R, Sinibaldi P, Rasi G, et al. Thymosin alpha1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo. Int Immunol. 2007;19:1261–1270. doi: 10.1093/intimm/dxm097.
  41. Yang X, Qian F, He HY, Liu KJ, Lan YZ, Ni B, Tian Y, Fu XL, Zhang J, Shen ZG, et al. Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro. Braz J Med Biol Res. 2012;45:25–32. doi: 10.1590/S0100-879X2011007500159.
  42. Nakama T, Hirono S, Moriuchi A, Hasuike S, Nagata K, Hori T, Ido A, Hayashi K, Tsubouchi H. Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality. Hepatology. 2001;33:1441–1450. doi: 10.1053/jhep.2001.24561.
  43. Chastre A, Belanger M, Beauchesne E, Nguyen BN, Desjardins P, Butterworth RF. Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in the progression of acute liver failure and its neurological complications. PLoS One. 2012;7:e49670. doi: 10.1371/journal.pone.0049670.
  44. Wang K. Molecular mechanisms of hepatic apoptosis. Cell Death Dis. 2014;5:e996. doi: 10.1038/cddis.2013.499.
  45. Zhang P, Shen H, Huang J, Wang H, Zhang B, Zhou R, Zhong B, Fan X. Intraperitoneal administration of fetuin-A attenuates D-galactosamine/lipopolysaccharide-induced liver failure in mouse. Dig Dis Sci. 2014;59:1789–1797. doi: 10.1007/s10620-014-3071-0.
  46. Romani L, Bistoni F, Montagnoli C, et al. Thymosin alpha1: an endogenous regulator of inflammation, immunity, and tolerance. Ann N Y Acad Sci. 2007;1112:326-38.
  47. Xu Y, Jiang Y, Wang L, et al. Thymosin Alpha-1 Inhibits Complete Freund’s Adjuvant-Induced Pain and Production of Microglia-Mediated Pro-inflammatory Cytokines in Spinal Cord. Neurosci Bull. 2019;35(4):637-648.
  48. Romani L, Oikonomou V, Moretti S, et al. Thymosin α1 represents a potential potent single-molecule-based therapy for cystic fibrosis. Nat Med. 2017;23(5):590-600.
  49. Carraro G, Naso A, Montomoli E, et al. Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study. Vaccine. 2012;30(6):1170-80.
  50. Ershler WB, Gravenstein S, Geloo ZS. Thymosin alpha 1 as an adjunct to influenza vaccination in the elderly: rationale and trial summaries. Ann N Y Acad Sci. 2007;1112:375-84.
  51. Panatto D, Amicizia D, Lai PL, Camerini R, De rosa A, Gasparini R. Utility of thymosin alpha-1 (Zadaxin) as a co-adjuvant in influenza vaccines: a review. J Prev Med Hyg. 2011;52(3):111-5.
  52. Xu YG, Guan XT, Liu ZM, Tian CY, Cui LC. Immunogenicity in Swine of Orally Administered Recombinant Lactobacillus plantarum Expressing Classical Swine Fever Virus E2 Protein in Conjunction with Thymosin α-1 as an Adjuvant. Appl Environ Microbiol. 2015;81(11):3745-52.
  53. Matteucci C, Grelli S, Balestrieri E, et al. Thymosin alpha 1 and HIV-1: recent advances and future perspectives. Future Microbiol. 2017;12:141-155. doi:10.2217/fmb-2016-0125.
  54. Wang G, He F, Xu Y, et al. Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias. Neurosci Bull. 2017;33(6):675-684. doi:10.1007/s12264-017-0162-x.
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