Thymic tissue is responsible for selected transformation of precursor cells into different T-cells, i.e. helper (CD4+) T-lymphocytes, which aid in the differentiation of other lymphocytes, killer cells (NK cells), cytotoxic cells, and suppressor (CD8+) T- lymphocytes (1-3). Having been released into the blood stream, intestinal and peripheral tissues, the lymphocytes are characterized by well-defined antigens or activation markers on their surface. Their activities are extra thymic.
The thymus is directly innervated, thus making its role in the interaction between the immune system and the neuroendocrinal systems understandable. In newborn mice, thymectomy causes a significant change and decrease of lymphatic tissue and a hypofunction of the Reticulo-Endothelial System (RES). In addition, the maturation of T-dependent lymphocytes is severely hampered, or even made impossible. The thymus produces a variety of substances, including thymus-specific enzymes, proteins, peptides and steroids, which all have both central and peripheral activities. Thymus peptides have a molecular weight of about 300-100,000 Dalton. Up to now, some peptide fractions have been isolated and identified, mainly from the thymus glands of young calves or foetus.
Thymus peptides also play an important role in the development, maturation, differentiation and activation of T-lymphocytes. In addition, thymus peptides enhance proliferation of precursors of lymphoid cells in bone marrow, and their maturation into T-lymphocytes.[i],[ii],[iii]
In a prospective randomized study in patients with malignant melanoma, thymus peptides caused an increased tumor-free period, a longer survival time and increased quality of life.[iv] In a prospective randomized study in intermediate- and high-grade Non-Hodgkins lymphoma, patients were treated with thymus peptides in addition to standard chemotherapy.
The treated patients tolerated thymus peptides quite well and had a significantly higher complete response rate than those patients who did not receive thymus peptides.[v] One prospective, randomized study in patients undergoing colorectal surgery showed that the patients who received thymus peptides in addition to Cefotetan did significantly better in lowering the rate of abdominal abscesses and upper respiratory tract infections.[vi]
One prospective, randomized study in women with advanced breast cancer could document that those women, receiving thymus peptides in addition to their chemotherapy regimen, tolerated the chemotherapy significantly better and reduced the rate of secondary infections.[vii],[viii] One prospective, randomized study in breast cancer patients showed that thymus peptides protect the bone marrow functions against the haematological toxicities and recovery during and after high dose of Mitoxantrone.[ix] Another study also showed significant benefit in complete response rate to therapy and prevention of myelosuppression and secondary infections when thymus peptides were added to the regimen.[x],[xi]
Therefore, in the Gorter Model, thymus peptides are used:
There is a delicate interaction between the thymus and the active bone marrow. There is a direct and positive correlation between hypofunction of the thymus and the decline of production of colony stimulating factors (CSF). Therefore, in cases where there is insufficient production of CSF, the therapeutic application of thymus peptides can be helpful.
Maurer, HR, Eckert, K, Stange, R: Einfluss der Therapie mit Thymoject auf die antitumorale Immunotoxizität der Leukozyten von Mamma-Tumorpatientinnen. Pers. Mitt. (1999). [ii] Mustacchi, G, Paves, L, Milani, S et al: High-dose folinic acid and fluouracil plus or minus thymostimulin for the treatment of metastatic colorectal cancer: results of a randomised multicentered trial. Anticancer Res. (1994) 14: 617-619. [iii] Schulof, RS, Loyd, MJ, Cleary, PA, et al: A randomized trial to evaluate the immunorestorative properties of synthetic thymosin-alpha1 in patients with lung cancer. J Biol Resp Modif (1985) 4: 147-158.[iv] Azizi A, Brenner HJ, Shoham J: Postoperative adjuvante Behandlung von Patienten mit malignem Melanom durch den Thymusfaktor Thymostimulin. Arzneim-Forsch/Drg Res (1984) 34(II): 1043-1046. [v] Massimo F, Gobbi P, Moretti G, Avanzini P, Italian Lymphoma Study Group: Effects of Thymostimulin with combination Chemotherapy in patients with aggressive non-Hogkins lymphoma. Am J Clin Oncol (CCT) (1995) 18(1): 8-14. [vi] Peretti P, Tonelli F, Mazzei T, Ficari F, Italian study group on antimicrobal prophylaxis in abdominal surgery. J Chemotherapy (1993) 5(1): 37-42. [vii] Gonelli S, Petrioli R, Cepollaro C, Palmieri R, Aquino A, Gennari C: Thymostimulin in association with chemotherapy in breast cancer patients with bone metastases. Clin Drug Invest (1995) 9(2): 79-87. [viii] Iaffaioli RV, Frasci G, Tortora G, Ciardiello F, Nuzzo F, Scala S, Pacelli R, Bianco AR: Effect of thymic extract Thymostimulin on the incidence of infections and myelotoxicity during adjuvant chemotherapy for breast cancer. Thymus (1988) 12: 69-75. Kluwer Academic Publishers. [ix] Sanchiz F, Milla A: A randomised study comparing granulocyte-colony stimulating factor (G-CSF) with G-CSF plus Thymostimulin in the treatment of haematological toxicity in patients with advanced breast cancer after high dose Mitoxantrone therapy. Eur J Cancer (1996) 32A(1): 52-56. [x] Macchaiarini 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 – 196.