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The thymus gland consists of two lobes, it is located behind the breastbone in front of the heart. To a large extent, the health of the thymus determines the health of the immune system. The thymus is a central lymphoid organ where bone marrow derived immature lymphocytes (a type of white cell) undergo differentiation and become active T-cell lymphocytes. They are called T-cells because they primarily mature in the thymus gland, although some also mature in the tonsils. T-lymphocytes, or T-cells, play a central role in cell-mediated immunity. The thymus changes its size and function during our life cycle. It is largest and most active in newborns, infants and in the years prior to adolescence. By the early teens, the thymus begins to shrink, and thymus tissue is replaced by fatty tissue. Nevertheless, a small amount of T-lymphocyte production and education continues throughout adult life. Lymphocytes make up roughly 20 to 40 percent of the total number of white blood cells.  Lymphocyte counts drop when bone marrow is suppressed during cytotoxic chemotherapy or radiation therapy. T-cells also decrease when the overall lymphocyte count drops.

 

The thymus produces enzymes and hormone-like peptides that play an important role in the development, maturation, differentiation, and activation of T-cells. Thymic peptides include thympoeitin, thymulin, thymosin, and thymic humoral factor, which all have both central and peripheral activities. Studies with thymic peptides have shown a variety of effects on the immune system. Basically, thymic peptides act as chemical messengers to activate, regulate, and stabilize the immune system. In clinical trials, thymus peptides strengthen the effects of immunomodulators in immunodeficiency, autoimmune diseases, and neoplastic malignancies.

 

There are two groups of injectable thymus products available for use in treatment:

  • Purified extracts from animal (mostly calf) thymus glands which contain peptides (pTE)

  • Synthetically produced thymus gland peptides (sTP)

 

Both injectable purified thymus extracts (pTE) and synthetic thymic peptides (sTP) have been demonstrated to enhance the immune system of cancer patients to assist in fighting tumor cell growth and resist infections due to immunosuppression induced by the disease and antineoplastic therapy. There are over 40 different factors in a purified thymus extract, that impart its therapeutic effectiveness, but not all have been adequately researched. For this reason, it is not advisable to only use individual thymus peptides, but rather the entire pTE, or in some cases a combination of the two. There are also oral extract forms of thymus (from bovine sources) in capsules and tablets sold as a dietary supplement. 

 

Generally, pTE has been demonstrated to have the following biological activities:

  • modulate the production, maturation and activation of T lymphocytes and improve B lymphocyte function

  • increase the number and function of T helper/inducer lymphocytes (T4 cells)

  • increase number function of T suppressor cells (T8 cells)

  • improve immune response through the enhancement of bone marrow function, and protect against bone marrow suppression from cytotoxic chemotherapy and radiation

  • prevent secondary infections due to immunosuppression caused by cytotoxic chemotherapy and surgical interventions

  • increase response rate of anticancer therapies through improvement of lymphocyte function and biological defense mechanisms

The following are selected articles on thymus therapy and thymic peptides.

Ba, D. E. N. I. A. N., et al. Restoration of T cell depression and suppression of blood pressure in spontaneously hypertensive rats (SHR) by thymus grafts or thymus extracts. The Journal of Immunology 128.3 (1982): 1211-1216.

Bach JF. 
Thymic hormones. J Immunopharmacol. 1979;1(3):277-310. 

Balbi B, Valle MT, Oddera S, and others. 
Thymomodulin increases release of granulocyte-macrophage colony stimulating factor and of tumour necrosis factor in vitro. European Respiratory Journal. October 1992; volume 5, number 9, pages 1097-1103.

 

Baxevanis, C. N., Reclos, G. J., Perez, S., Kokkinopoulos, D., & Papamichail, M. (1987). Immunoregulatory effects of fraction 5 thymus peptides. I. Thymosin α1 enhances while thymosin β4 suppresses the human autologous and allogeneic mixed lymphocyte reaction. Immunopharmacology, 13(2), 133-141.


Bodey B, Bodey B Jr, Siegel SE, Kaiser HE. Review of thymic hormones in cancer diagnosis and treatment. Int J
Immunopharmacol. 2000 Apr;22(4):261-73.

Bos, R. et al. 
Expression of a natural tumor antigen by thymic epithelial cells impairs the tumor-protective CD4+ T-cell
repertoire.
 
Cancer Res. 65, 6443–6449 (2005).

Cangemi, V.; Volpino, P.; D’Andrea, N.; Gentili, S.; Ippoliti, F.; Piat. G. 
Thymostimulin effect on the immune response in
neoplastic patients submitted to surgical treatment.
 Panminerva Medica 1993, 35:218-23.

Cohen MH, Chretien PB, Ihde DC, et al. 
Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small cell lung cancer. JAMA 1979;241:1813-5.


Fiocchi A, Borella E, Riva E, et al. Double-blind clinical trial for the evaluation of the therapeutical effectiveness of a calf thymusderivative (Thymomodulin) in children with recurrent respiratory infections. Thymus 1986; 8:331-9.

 

Fiorilli M, Sirianni MC, Pandolfi F, Quinti I, Tosti U, Aiuti F, Goldstein G. Improvement of natural killer activity and of T cells after thymopoietin pentapeptide therapy in a patient with severe combined immunodeficiency. Clin Exp Immunol. 1981 Aug; 45(2): 344-51.

Garbin F, Eckert K, Buttner P, Garbe C, Czarnecki J, Maurer H. 
The influence of the thymic preparation thymex-L on deficient antitumor-activity of monocytes from melanoma patients in-vitro. Oncol Rep. 1995 May;2(3):469-72.

Goldstein AL, Thurman GB, Rossio JL, Costanzi JJ. 
Immunologic reconstitution of patients with primary immunodeficiency diseases and cancer after treatment with thymosin. Transplant Proc. 1977 Mar;9(1):1141-4.

Goldstein AL. The Gordon Wilson lecture. 
The history of the development of thymosin: chemistry, biology and clinical
applications.
 Trans Am Clin Climatol Assoc. 1977;88:79-94.

 

Hager, E. D., and D. Höhmann. "Comprehensive compilation of clinical studies with thymic peptides in oncology." AKTUELLE ONKOLOGIE 96 (1997): 176-182.


Incefy GS, Boumsell L, Kagan W, Goldstein G, Sousa MD, Smithwick E, O’Reilly R, Good RA. Enhancement of T lymphocyte differentiation in vitro by thymic extracts and purified polypeptides in severe combined immunodeficiency diseases. Trans Assoc Am Physicians. 1975;88:135-45.

Incefy GS, O’Reilly RJ, Kapoor N, Iwata T, Good RA. 
In vitro differentiation of human marrow T cell precursors by thymic
factors in severe combined immunodeficiency.
 Transplantation. 1981 Oct;32(4):299-305.

Kouttab, N.M.;Prada, M.; Cazzola, P. 
Thymomodulin: biological properties and clinical applications. Medical Oncol. & Tumor Pharmacother. 1989, 6:5.

Lantero S, Oddera S, Silvestri M, Ottolini V, Sacco O, and Rossi GA. Division of Pneumology, G. Gaslini Institute, Genoa, Italy.

Thymomodulin enhances phagocytic and intracellular killing activities of polymorphonuclear leucocytes without increasing release of chemotactic factors. Monaldi Arch. Chest Dis. 1993; volume 48, number 1, pages 29-33.

Liberati AM, Ballatori E, Fizzotti M, et al. 
A randomized trial to evaluate the immunorestorative properties of thymostimulin in
patients with Hodgkin's disease in complete remission.
 Cancer Immunol.Immunother. 1988;26(1):87-93.

Low TL, Thurman GB, Chincarini C, McClure JE, Marshall GD, Hu SK, Goldstein AL. 
Current status of thymosin research:  evidence for the existence of a family of thymic factors that control T-cell maturation. Ann N Y Acad Sci. 1979;332:33-48.

Macchiarini P, Danesi R, Del Tacca M, Angeletti CA. 
Effects of thymostimulin on chemotherapy-induced toxicity and long-term survival in small cell lung cancer patients. Anticancer Res 1989;9:193-6.

 

Mayer, Gerd, K. Pohlmeyer, Alexander Caliebe, Edgar Heimueller, Bert Behnke, Garnet Steimann, Claudia Lange, and Josef Beuth. "Low molecular thymic peptides stimulate human blood dendritic cells." Anticancer research 20, no. 5A (2000): 2873-2883.

Morozov, V. G., and V. Kh Khavinson. "Natural and synthetic thymic peptides as therapeutics for immune dysfunction." International journal of immunopharmacology 19, no. 9-10 (1997): 501-505.
 

Mutchnick, Milton G., Henry D. Appelman, H. T. Chung, Emma Aragona, Tej P. Gupta, Glen D. Cummings, Jeanne G. Waggoner, Jay H. Hoofnagle, and David A. Shafritz. "Thymosin treatment of chronic hepatitis B: a placebo‐controlled pilot trial." Hepatology 14, no. 3 (1991): 409-415.

Naylor, Paul H., and Milton G. Mutchnick. Thymus-derived peptides in the treatment of viral chronic hepatitis. Digestive Diseases 14.6 (1996): 362-370.

 

Novoseletskaya, A. V., N. M. Kiseleva, I. V. Zimina, O. V. Belova, A. N. Inozemtsev, V. Ya Arion, and V. I. Sergienko. "Stress-protective effect of thymic peptides." Bulletin of experimental biology and medicine 158, no. 6 (2015): 753.

Lunin, Sergey M., and Elena G. Novoselova. "Thymus hormones as prospective anti-inflammatory agents." Expert Opinion on Therapeutic Targets 14, no. 8 (2010): 775-786.

Reggiani, Paula C., Gustavo R. Morel, Gloria M. Cónsole, Claudio G. Barbeito, Silvia S. Rodriguez, Oscar A. Brown, Maria Jose Bellini, Jean-Marie Pléau, Mireille Dardenne, and Rodolfo G. Goya. "The thymus–neuroendocrine axis: physiology, molecular biology, and therapeutic potential of the thymic peptide thymulin." Annals of the New York Academy of Sciences 1153 (2009): 98.

C Reggiani, Paula, Jose I Schwerdt, Gloria M Console, Eduardo A Roggero, Mireille Dardenne, and Rodolfo G Goya. "Physiology and therapeutic potential of the thymic peptide thymulin." Current pharmaceutical design 20, no. 29 (2014): 4690-4696.

Schulof, Richard S., and Stephen Davis. "Thymic peptide hormones: basic properties and clinical applications in cancer." Critical reviews in oncology/hematology 3, no. 4 (1985): 309-376.

Skotnicki, A.B. Therapeutic application of calf thymus extract TFX. Medical Oncol. & Tumor Pharmacother. 1989, 6:31.

Sztein, Marcelo B., Susana A. Serrate, and Allan L. Goldstein. "Modulation of interleukin 2 receptor expression on normal human lymphocytes by thymic hormones." Proceedings of the National Academy of Sciences 83, no. 16 (1986): 6107-6111.


Terrizzi A, Di Somma C, Dato D, Sandri MT, Cazzola P, and Berti Riboli E. Thymomodulin prevents post-operative
immunodepression measured by means of skin tests.
 International Journal of Immunotherapy. 1988; volume 4, number 3, pages 193-198.

Twomey, J.J. and Kouttab, N.N.L. 
Selected phenotypic induction of null lymphocytes from mice with thymic and nonthymic agents. Cell Immun. 1982, 72:186.

Vucković-Dekić LJ1, Susnjar S, Stanojević-Bakić N, Rajner L, Frim O. 
The protective activity of Thymex L against
radiotherapeutically-induced cellular immunodepression in lung cancer patients.
 Neoplasma. 1992;39(3):171-6.

Wolf E, Milazzo S, Boehm K, Zwahlen M, Horneber M. 
Thymic peptides for treatment of cancer patients. Cochrane Database Syst Rev. 2011 Feb 16; (2):CD003993. Epub 2011 Feb 16.

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