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Thymosin Alpha
Wednesday, August 14th, 2019

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 [1-5]
  • Boosts the function of certain immune cells [6-13]
  • Suppresses cancer and tumor growth [14-15]
  • Accelerates the wound healing process [3,26-27]
  • Increases vaccine effectiveness [37-40]

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]
  3. In mice with fungal infection, thymosin alpha 1 increased the production of phagocytes, which are cells capable of engulfing and absorbing bacteria. [3]
  4. Thymosin alpha 1-based immunomodulatory therapy was associated with a significant reduction in mortality in septic patients.[4]
  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. [5]

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. [6-7]
  2. Thymosin alpha 1 also helps regulate both the innate and adaptive immune systems. [8-9]
  3. Thymosin alpha has the ability to increase CD4+/CD8+ ratio. [10-11]
  4. By activating and stimulating certain signaling pathways, thymosin alpha 1 boosts the production of immune-related cytokines. [12]
  5. By selectively stimulating the release of luteinizing hormone (LH), thymosin alpha 1 indirectly strengthens the immune function. [13]

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. [14]
  2. In stage IV human breast cancer model, thymosin alpha 1 treatment was associated with significantly slow tumor growth. [15]
  3. In patients with metastatic melanoma and advanced non-small cell lung cancer, thymosin alpha 1 treatment prolonged survival. [16]
  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. [17]
  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. [18-20]
  6. Administration of thymosin alpha 1 in cancer patients was associated with reduced risk of dying and improved disease‐/progression‐free survival. [21]
  7. In patients with metastatic lung cancer, thymosin alpha 1 treatment was associated with complete disappearance of lesions. [22]
  8. A cell study found that exposure of human breast cancer cells to thymosin alpha 1 induced apoptosis (programmed cell death). [23]
  9. Administration of thymosin alpha 1 in cancer patients increased the anti-tumor effect of chemotherapy while markedly reducing side effects of the treatment. [24]
  10. In tumor-bearing mice, thymosin alpha 1 significantly delayed tumor growth and prolonged survival time. [25]

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. [26]
  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. [27]
  3. In rat kidney cells, thymosin alpha 1 prevented programmed cell death and renal scarring. [3]

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. [28]
  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. [29-31]
  3. Thymosin alpha 1 also reduces inflammation by suppressing pro-inflammatory TNF-α. [32-35]
  4. A cell-based study also found that thymosin alpha 1 protects against inflammatory allergy. [36]

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. [37]
  2. In elderly patients, administration of thymosin alpha 1 together with influenza vaccine enhanced vaccine responses. [38-39]
  3. In animal models, thymosin alpha 1 enhanced the efficacy of the classical swine fever vaccine. [40]

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. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. King R, Tuthill C. Immune Modulation with Thymosin Alpha 1 Treatment. Vitam Horm. 2016;102:151-78.
  13. Milenkovic L, Mccann SM. Effects of thymosin alpha-1 on pituitary hormone release. Neuroendocrinology. 1992;55(1):14-9.
  14. 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.
  15. Shrivastava P, Singh SM, Singh N. Activation of tumor-associated macrophages by thymosin alpha 1. Int J Immunopathol Pharmacol. 2004;17(1):39-47.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. Wolf E, Milazzo S, Boehm K, Zwahlen M, Horneber M. Thymic peptides for treatment of cancer patients. Cochrane Database Syst Rev. 2011;(2):CD003993.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. Available from https://www.federallabs.org/technology/thymosin-alpha-1-promotes-tissue-repair-angiogenesis-and-cell-migration.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. Wang K. Molecular mechanisms of hepatic apoptosis. Cell Death Dis. 2014;5:e996. doi: 10.1038/cddis.2013.499.
  35. 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.
  36. 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.
  37. 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.
  38. 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.
  39. 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.
  40. 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.
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